Role of ancillary techniques in diagnosis, therapy and prognosis of a case of precursor B-cell acute lymphoblastic leukemia in an elderly patient

The chromosomal abnormality of Philadelphia chromosome is mostly seen in Chronic Myeloid Leukemia (CML). But it is observed that the Philadelphia chromosome (Ph), t(9,22), is the most common cytogenetic abnormality in adult patients with acute lymphoblastic leukemia (ALL), occurring in about 20% to 30 % of all cases. Patients with Ph-positive ALL have breaks in the minor breakpoint region, m?BCR (exons 1?2) lead to a short fusion proteins (p190) and is most frequently associated with Ph chromosome- positive ALL. They have an increased risk for central nervous system (CNS) involvement, an aggressive clinical course and poor prognosis. Historically, they had an inferior outcome when compared with their Ph-negative counterparts. Adult Ph+ patients achieve Complete Remission rates comparable to Ph? ALL patients with standard chemotherapy, but the remissions are short and survival poor. The addition of tyrosine kinase inhibitors (TKIs) including imatinib has dramatically improved outcomes. We are presenting this case report of t(9;22), p190 BCR-ABL1 positive ALL in an elderly female patient of south Gujarat.

Chronic myeloid leukemia with a significant increase of monocytes and rare karyotype: A case report and literature review / 中南大学学报(医学版)

Chronic myeloid leukemia with a significant increase of monocytes is rare and difficult to identify from chronic myelo-monocytic leukemia in clinic. A 31-year-old male patient with systemic pain was initially diagnosed as chronic myelo-monocytic leukemia, who was finally diagnosed as chronic myeloid leukemia by fusion gene and chromosome examination. In addition to the typical Ph chromosome, a rare chromosome translocation t(2; 7)(p13; p22) was observed. The detection of monocyte subsets by multi-parameter flow cytometry is a diagnostic marker to distinguish the above 2 diseases. The relationship between fusion genes and mononucleosis is not clear. Tyrosine kinase inhibitors or allogeneic hematopoietic stem cell transplantation can be used in the treatment for this disease.

Rare type I CBFβ/MYH11 fusion transcript in primary acute myeloid leukemia with inv(16)(p13.1q22): a case report

Inv(16)(p13.1q22) in acute myeloid leukemia (AML) is a common chromosomal abnormality. It leads to the core-binding factor ß-subunit (CBFβ)/smooth muscle myosin heavy chain 11 (MYH11) fusion gene. Different breakpoints were observed in the CBFβ gene at 16q22 and the MYH11 gene at 16p13.1. For this reason, different CBFβ/MYH11 fusion genes are generated, with more than 13 types having been reported to date. Type I CBFβ/MYH11 fusion transcripts are very rare, with only 10 cases being reported to date. This case report describes a primary AML patient with inv(16)(p13.1q22) and a rare type I CBFβ/MYH11 fusion gene. The morphological analysis did not conform to the typical M4eo. Abnormal eosinophils were less than 5%, and there was obvious dysgranulopoiesis. The patient was in hematological and genetic remission for 487 days after the initial chemotherapy cycles. However, the CBFβ/MYH11 fusion had been constantly positive. Moreover, the presence of non-type A fusions may affect its biology and clinical prognosis. Therefore, further studies on understanding its biological and prognostic significance are essential.

Epidemiology and Patterns of Leukemia in Northern Saudi Arabia

Objective: The aim of the present study was to determine the patterns of leukemia in Northern Saudi Arabia. Methodology: This was a retrospective descriptive study conducted in King Khalid hospital, Hail, Kingdom of Saudi Arabia (KSA) including records of leukemia from 2008 to 2016. Results: The overall Crude Incidence Rate (CIR) of leukemia was 7.45 per 100.000 person-year, including patients diagnosed with different patterns of leukemia in Northern Saudi Arabia. The mean age of patients was 45.4 years with a minimum of 5 years and a maximum of 107 years old. Around 43 (59%) were males and 30 (41%) were females. Conclusion: The incidence rates of leukemia are relatively higher in Northern Saudi Arabia, with an increase of all subtype.

Effect of down-regulation of MLAA-22 gene on proliferation and differentiation of U937 cells / 西安交通大学学报(医学版)

Objective To explore the effect of down-regulation of MLAA-22 gene on proliferation and differentiation of U937 cells.Methods MLAA-22 gene was down-regulated by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9)system in U937 cells.The activity of single guide RNA (sgRNA)was detected by CruiserTMenzyme digestion assay.The mutation rate of MLAA-22 gene was analyzed by TA cloning and sequencing assay of PCR products of the gene mutation region.Cell proliferation was evaluated by CCK-8 assay.Expression of CD11b was tested by flow cytometry to evaluate cell differentiation. Results CruiserTMenzyme digestion assay showed the sgRNA of the CRISPR/Cas9 system identified the target spot efficiently.TA cloning and sequencing assay displayed the mutation rate of MLAA-22 gene was 61.3%.CCK-8 assay demonstrated that the proliferation was obviously inhibited in MLAA-22-knockdown U937 cells.In addition, flow cytometry assay indicated CD11b-positive cells significantly increased in MLAA-22-knockdown U937 cells. Conclusion MLAA-22 gene regulates the proliferation of U937 cells probably by regulating their differentiation, thus promoting the occurrence and development of acute monocytic leukemia.

Screening and identification of RNA interference sequence for human acute monocytic leukemia related antigen 22 / 白血病·淋巴瘤

Objective To screen the optimal RNA interference sequence of acute monocytic leukemia associated antigen 22 (MLAA-22) gene in order to study gene function of it. Methods MLAA-22 coding sequence (CDS) was cloned by reverse transcription polymerase chain reaction (RT-PCR) and the CDS was inserted in to pEGFP-N1-3FLAG vector to construct eukaryotic expression vector of MLAA-22. At the same time, four RNA interference sequences were designed and cloned to the vector. Expression vector and RNA interference vector were co-transfected into 293T cells, and the optimal RNA interference sequence was screened by fluorescence and Western blot analyses. Results MLAA-22 eukaryotic expression vector pEGFP-N1-3FLAG and four RNA interference vectors were successfully constructed. After co-transfected 293T cells, KD2 was selected as the optimal interference sequence of MLAA-22. Conclusion KD2 is an optimal interference sequence for targeting MLAA-22 antigen gene.

Function and mechanism of TRIM22 targeting eIF4E in the process of NB4 cells differentiation / 国际肿瘤学杂志

Objective To investigate the function of tripartite motif protein 22 (TRIM22) and the interaction with eukaryotic translation initiation factor-4E (eIF4E) in the differentiation of NB4 cells, one kind of acute promyelocytic leukemia cells, which elucidates the mechanism of TRIM22 targeting to regulate eIF4E.Methods The model of NB4 cells inducing differentiation was established in vitro.The expression changes of gene and protein of TRIM22 and eIF4E were detected by using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting.In addition, the effect on cell function and protein expression level of eIF4E after adopting electroporation technology to depress or over-express TRIM22 was detected by CCK-8 and flow cytometry.Finally, the interaction of TRIM22 and eIF4E was verified by using co-immunoprecipitation (CO-IP).Results The mRNA relative expression level of TRIM22 was gradually increasing from 1.01±0.15 to 30.98±2.79 (F=280.700, P=0.000), and the protein relative expression level was gradually increasing from 0.22±0.03 to 0.51±0.05 (F=51.430, P=0.000) after the all-trans-retinoic acid (ATRA) induction for NB4 cell.However, the mRNA relative expression level of eIF4E was gradually decreasing from 1.01±0.09 to 0.47±0.06 (F=20.520, P=0.000), with the same trend, the protein relative expression level was gradually decreasing from 0.97±0.02 to 0.64±0.09 (F=14.700, P=0.001).The expression level of PE-CD11b in the TRIM22 over-expression group with ATRA detected by flow cytometry [(78.80±2.00)%] was higher than that in the transfection group of empty vetor with ATRA [(58.70±2.70)%] (t=9.535, P=0.000) and the cotransfection group with ATRA [(61.60±3.80)%] (t=8.187, P=0.000).Meanwhile, the protein level of eIF4E changed reversely after over-expressing the gene level of TRIM22 (t=4.985, P=0.007).The CO-IP experiment was used to verify the interaction of TRIM22 and eIF4E.ConclusionTRIM22 is able to promote the cell differentiation during the process of NB4 cells differentiation.Furthermore, eIF4E is a target of TRIM22 for binding with, which plays an important role in depressing the expression of eIF4E.

Establishment and verification of a KCL22/NOD-SCID mouse transplantation tumor model of chronic myeloid leukemia / 中国实验动物学报

Objective To investigate the potential of chronic myeloid leukemia ( CML) cell line KCL22 in indu-cing leukemia in NOD-SCID mice for setting up a basis for constructing a CML mouse transplantation tumor model. Methods 2 ×107 KCL22 cells in logarithmic growth phase were injected via the tail vein into experimental NOD-SCID mice whereas PBS was injected to the mice of control group.General condition of the mice of both groups was observed.Wright staining was used to observe the changes of blood and bone marrow smears.PCR was conducted to detect the transcription level of BCR-ABL, and histology with HE staining was used to evaluate the tumor cell invasion in the liver and spleen. Results Four weeks after the injection of KCL22 cells, the mice in experimental group showed physical signs of decreased reactivity, depression, swollen hindlimb muscles and petechia on the hindlimb femur.Peripheral white blood cells ( WBC) began to increase after 5 weeks, with a significantly increased quantity compared with the control group (P90 days) (P<0.05).Conclusions A NOD-SCID mouse model of CML transplantation tumor is successfully established with leukemia KCL22 cells.

Effects of ABL SH3-T79Y mutant combined with imatinib on the proliferation of chronic myeloid leukemia cells / 解放军医学杂志

Objective To analyze the influence of SH3 domain mutant (ABL SH3-T79Y) in BCR-ABL protein of chronic myeloid leukemia (CML) in combination with imatinib (IM) on the proliferation of CML cells in vivo and vitro, and to discuss the mechanism thereof. Methods Recombinant ABL SH3-T79Y mutant adenovirus vectors which were successfully constructed in previous work was used with IM to treat K562/G01 cells, then the cell-colony forming ability of K562/G01 cells was determined by clone formation assay, and cell cycle was assessed by flow cytometry. KCL22 cells were treated by recombinant SH3-T79Y and IM to construct subcutaneous solid tumor model in Balb/c nude mice, then the formation rate of subcutaneous tumor was estimated, the pathological examination was conducted, and the proliferation ability of KCL22 cells was assayed. K562/G01 cells were treated by SH3-T79Y and IM in combination, and the expression levels of p-BCR-ABL, BCR-ABL, p-CrkL, CrkL and Cyclin-D1 protein were determined by Western blotting. Cells treated with PBS, null recombinant adenovirus vectors or IM alone served as control groups. Results Compared to the 3 control groups, clone forming rate of K562/G01 cells decreased significantly (P<0.05) and cell cycles were arrested at S phase after being combined SH3-T79Y and IM treatment. The subcutaneous solid tumor formation rate in KCL22- Balb/c nude mice was 16.7% after combined SH3-T79Y and IM treatment, and large number of tumor cells were observed in tumor pathology examination. Western blotting revealed that the expression levels of p-BCR-ABL, p-CrkL, BCR-ABL, CrkL and Cyclin-D1 were decreased in K562/G01 cells. Conclusion Combined treatment of SH3-T79Y and imatinib may inhibit the proliferation of CML cells in vivo and in vitro by decreasing BCR-ABL and CrkL phosphorylation as well as Cyclin-D1 protein.

Estudo da expressão dos genes ABCB1 e SLC22A1 e sua relação com marcadores de resposta ao mesilato de imatinibe em pacientes com leucemia mieloide crônica / Study of the expression of SLC22A1 and ABCB1 genes and their relationship with markers of response to imatinib mesylate in patients with chronic myeloid leukemia

A leucemia mieloide crônica (LMC) é uma expansão clonal da célula tronco hematopoética, traduzindo-se por hiperplasia mieloide, leucocitose, neutrofilia, basofilia e esplenomegalia. O cromossomo Filadélfia é característico da doença, sendo produto da translocação t(9:22)(q34;q11), resultando na fusão dos genes ABL e BCR. Esta fusão gera um gene híbrido que codifica uma proteína com elevada atividade tirosinoquinase e tem um papel central na patogenia da LMC. O mesilato de imatinibe (MI) é um derivado da fenilaminopirimidina que inibe a proteína tirosinoquinase BCR-ABL1 in vitro e in vivo. O MI interage com transportadores de membrana de influxo, como o organic carion solute carrier 22 ,member 1 (SLC22A1,hOCT1); e de efluxo, como ATP binding cassette B1 (ABCB1, MDR1, P-gp). Os polimorfismos ABCB1 c.1236C>T, C.3435C>T e c.2677G>T/A têm sido associados com a alteração da função da P-gp. Este estudo teve por objetivo investigar a relação da expressão do RNAm de ABCB1 e SLC22A1 com marcadores de resposta ao tratamento com MI e avaliar a atividade funcional da P-gp em células mononucleares de pacientes com diferentes haplótipos para os polimorfismos ABCB1 c.1236C>T, c.3435C>T e c.2677G>T/A. Foram incluídos 118 pacientes com LMC para o estudo da expressão do RNAm de SLC22A1 e ABCB1 e para o estudo da atividade da P-gp foram selecionados 28 pacientes de acordo com os haplótipos dos polimorfismos ABCB1 c.1236C>T, c.3435C>T e c.2677G>T/A. Para o estudo da expressão do RNAm de SLC22A1 e ABCB1 foram constituídos dois grupos: Grupo 1 com 70 pacientes com resposta citogenética completa com a dose padrão de MI (400 mg/dia de MI) em até 18 meses e, Grupo 2 com 48 pacientes sem resposta citogenética completa com a dose inicial de 400 mg/dia de MI ou que perderam esta resposta ao longo do tratamento. Para o estudo da atividade funcional da P-gp, dos 118 pacientes incluídos, foram selecionados 10 pacientes que apresentaram o haplótipo 1236CC/3435CC/2677GG, 10 pacientes que apresentaram o haplótipo 1236CT/3435CT/2677GT e 8 pacientes que apresentaram o haplótipo 1236TT/3435TT/2677TT. A resposta ao tratamento foi avaliada segundo os critérios da European LeukemiaNet. Amostras de sangue foram obtidas para: quantificação de BCR-ABL1, extração do RNAm total, análise citogenética de banda G, dosagem da concentração plasmática de MI e análise da atividade e expressão da P-gp. A análise da expressão dos genes ABCB1 e SLC22A1 foi feita por PCR em tempo real, a análise da atividade e expressão da P-gp foram feitas por citometria de fluxo e a dosagem da concentração plasmática de MI foi realizada por eletroforese capilar. Resultados: A expressão de ABCB1 e SLC22A1 foi analisada nos 118 pacientes incluídos e foi similar entre os grupos de resposta. A elevada expressão do gene SLC22A1 foi associada àqueles pacientes que alcançaram a resposta molecular maior (RMM) no grupo respondedor (P=0,009). Não houve associação entre a expressão de ABCB1 e a resposta ao MI. Nenhum dos genes foi associado à resposta molecular completa (RMC). No estudo da atividade da P-gp foi observada uma maior atividade nos pacientes que apresentavam o haplótipo 1236CC/3435CC/2677GG quando comparado àqueles que possuíam o haplótipo com alelo mutado. Não houve diferença na expressão do RNAm dos genes SLC22A1 e ABCB1, expressão da P-gp e concentração plasmástica de MI entre os grupos de haplótipos. Os pacientes que não alcançaram a RMM apresentaram uma maior taxa de efluxo mediado pela P-gp quando comparado aos indivíduos que alcançaram esta resposta (64,7% vs. 45,7%; P=0,001). Os indivíduos que alcançaram a RMM e RMC apresentaram maior mediana de expressão do gene SLC22A1. Os pacientes sem RMM apresentaram menor concentração plasmática de MI quando comparados aos que alcançaram esta resposta (0,51 µg/mL vs. 1,42 µg/mL; P=0,001). Não foi observada associação entre a concentração plasmática de MI e a RMC. Em conclusão os pacientes respondedores a dose padrão de 400mg/dia de MI e que alcançaram a RMM apresentam maior expressão de RNAm de SLC22A1 e os portadores dos haplótipos 1236CT/3435CT/2677GT e 1236TT/3435TT/2677TT exibem menor efluxo mediado pela P-gp apresentando maior frequência de RMM

Chronic myeloid leukemia (CML) is a clonal expansion of hematopoietic stem cell, translating into myeloid hyperplasia, leukocytosis, neutrophilia, basophilia and splenomegaly. The Philadelphia chromosome is characteristic of the disease, being the product of the translocation t(9:22)( q34,q11), resulting in the fusion of the BCR and ABL genes. This fusion generates a hybrid gene that encodes a protein with elevated tyrosine kinase activity and plays a central role in the pathogenesis of CML. Imatinib mesylate (IM) is a derivative of fenilaminopirimidine that inhibits BCR-ABL1 fusion protein tyrosine kinase in vitro and in vivo. IM interacts with uptake membrane transporters, such as cation organic solute carrier 22, member 1 (SLC22A1, hOCT1) and efflux as ATP binding cassette B1 (ABCB1, MDR1,P-gp). ABCB1 polymorphisms c.1236C>T,c.3435C>T and c.2677G>T/A have been associated with altered function of P-gp. This study aimed to investigate the relationship between mRNA expression of ABCB1 and SLC22A1 with markers of response to treatment with IM and evaluate the functional activity of P-gp in mononuclear cells of patients with different haplotypes for ABCB1 c.1236C>T, c.3435C>T and c.2677G>T/A polymorphisms. This study included 118 patients with CML to study the mRNA expression of SLC22A1 and ABCB1 and to study the P-gp activity, 28 patients were selected according to the haplotypes of ABCB1 c.1236C>T, c.3435C>T and c.2677G>T/A polymorphisms. To study the mRNA expression of SLC22A1 and ABCB1, two groups were constituted: Group 1 with 70 patients with a complete cytogenetic response with standard-dose IM (400 mg/day) in 18 months, and group 2 with 48 patients without complete cytogenetic response with the initial dose of IM (400 mg/day) or have lost this response during treatment. To study the P-gp functional activity, 10 patients with haplotype 1236CC/3435CC/2677GG, 10 patients with haplotype 1236CT/3435CT/2677GT and 8 patients with haplotype 1236TT/3435TT/2677TT were enrolled. Treatment response was assessed according to European LeukemiaNet criteria. Blood samples were obtained for: quantification of BCR-ABL1, mRNA extraction, G band cytogenetic analysis, measurement of IM plasma levels and P-gp activity and expression. The ABCB1 and SLC22A1 gene expression analysis was made by real-time PCR, analysis of P-gp activity and protein expression were performed by flow cytometry and determination of plasma Levels of IM was performed by capillary electrophoresis. Results: Expression of ABCB1 and SLC22A1 were analyzed in 118 patients included and was similar between the response groups. Higher expression of the SLC22A1 gene was associated with those patients who achieved a major molecular response (MMR) in the responder group (P=0.009). There was no association between ABCB1 expression and IM response. None of the studied genes was associated with complete molecular response (CMR). In the study of P-gp activity we observed greater activity mediated by P-gp in patients with 1236CC/3435CC/2677GG haplotype when compared to those with the mutated allele. There was no difference in mRNA expression of SLC22A1 and ABCB1 genes, P-gp expression and IM plasma levels between haplotypes groups. Patients who did not achieve MMR showed a higher rate of efflux mediated by P-gp compared to individuals who did achieve this response (64.7% vs. 45.7%, P=0.001). Individuals who achieved MMR and CMR had higher median of SLC22A1 expression. Patients without MMR had lower IM plasma levels compared with those who achieved this response (0.51 µg/mL vs. 1.42 µg/mL, P=0.001). No association was observed between IM plasma levels and CMR. In conclusion patients responders to standard dose of IM (400 mg/day) and who achieved MMR have higher SLC22A1 mRNA expression and the carriers of 1236CT/3435CT/2677GT 1236TT/3435TT/2677TT haplotypes exhibit lower efflux mediated by P-gp with higher frequency of MMR

Characteristics of hematologic malignancies with coexisting t(9;22) and inv(16) chromosomal abnormalities

BACKGROUND: The coexistence of t(9;22)(q34;q11.2) and inv(16)(p13q22) chromosomal abnormalities is extremely uncommon, and only a small number of such cases have been reported. Here, we characterized 7 cases of hematologic malignancy exhibiting t(9;22) and inv(16) coexistence. METHODS: We reviewed the cytogenetic data for hematologic malignancies treated at the Catholic Blood and Marrow Transplantation Center between January 2004 and June 2013. We identified 7 cases exhibiting t(9;22) and inv(16) coexistence. In addition, we analyzed mutations in the IKZF1, NPM1, FLT3, N-RAS, K-RAS, c-KIT, and TP53 genes. RESULTS: Four cases of chronic myelogenous leukemia (CML; 1 chronic phase, 2 accelerated phase, and 1 blast phase) and 3 cases of acute myeloid leukemia (AML; 1 de novo and 2 therapy-related) were identified. The percentages of circulating blasts and bone marrow eosinophils were higher in AML cases than in CML cases (53% vs. 5% and 30% vs. 5.5%, respectively). The proportions of each chromosomal abnormality were used along with follow-up karyotyping results to identify secondary changes. In BCR/ABL, a p210 fusion transcript was associated with CML, whereas a p190 fusion transcript was associated with AML. One patient with AML harbored 2 mutations: c-KIT D816V and TP53 E11Q. All patients except 1 with CML blast phase sustained clinical remission after treatment, which included an imatinib mesylate regimen. CONCLUSION: This study shows that observations of bone marrow morphology, initial and follow-up cytogenetic studies, and karyotyping of BCR/ABL1 and CBFB/MYH11 provide valuable information for characterizing hematologic malignancies exhibiting t(9;22) and inv(16) coexistence.

A Case of Adult B Lymphoblastic Leukemia with ider(9)(q10)t(9;22)(q34;q11.2) and der(19)t(1;19)(q23;p13.3) / 대한진단검사의학회지

In B lymphoblastic leukemia/lymphoma (B-ALL/LBL), t(9;22)(q34;q11.2) and t(1;19)(q23;p13.3) are recurrent cytogenetic abnormalities. The concurrent occurrence of both abnormalities is very rare, and only 3 cases have been previously reported. Here, we report a case of adult B-ALL with ider(9)(q10)t(9;22)(q34;q11.2) and der(19)t(1;19)(q23;p13.3). A literature review revealed that ider(9) (q10)t(9;22) is a rare variant of t(9;22) with a deletion of the short arm of chromosome 9. Fifteen cases of ider(9)(q10)t(9;22) have been reported. This abnormality is specific to precursor B-lymphoid neoplasms, such as B-ALL or B-lymphoid blast phase of CML, and is associated with disease progression or short survival. The cytogenetic abnormality t(1;19) is also specific to B-ALL. In most instances of t(1;19), TCF3 is fused to PBX1; however, a few cases have identical translocations but no TCF3-PBX1 fusion, as was observed in our patient. We describe the first case of ider(9)(q10)t(9;22) in combination with TCF3-PBX1 negative t(1;19). The patient underwent imatinib therapy in addition to intensive chemotherapy, but failed to achieve remission.

Two Cases of Acute Myeloid Leukemia with t(16;21)(p11;q22) and TLS/FUS-ERG Fusion Transcripts / 대한진단검사의학회지

Many AML-associated chromosomal abnormalities, such as t(8;21), t(15;17), inv(16), t(9;11), t(9;22) and t(6;9) are well known. The chromosomal aberration of t(16;21)(p11;q22) in AML is rare and it is known to be associated with poor prognosis, young age (median age, 22 yr), and involvement of various subtypes of the French-American-British classification. We report here 2 AML patients with t(16;21)(p11;q22), proved by conventional cytogenetics and/or reverse transcription (RT)-PCR. Erythrophagocytosis by leukemic blasts was observed in both of the cases. One patient was a 24 yr-old male with acute myelomonocytic leukemia. His karyotype was 46,XY,t(16;21)(p11;q22),del(18)(p11.2) and RT-PCR revealed the TLS/FUS-ERG fusion transcripts. Although he received allogeneic peripheral blood stem cell transplantation after the first remission, he died 9 months after the initial diagnosis due to relapse of the disease and graft-versus-host disease. The other patient was a 72 yr-old male with acute myeloid leukemia without maturation. His karyotype was 45,XY,-16,add(21)(q22) and the presence of t(16;21)(p11;q22) was detected by RT-PCR. He was transferred to another hospital with no more follow-up. We suggest that the presence of t(16;21)(p11;q22) and/or TLS/FUS-ERG fusion transcripts has to be considered in cases of AML with erythrophagocytosis.

t(9;22) with 5'ABL1 Deletion and t(6;19) in Biphenotypic Acute Leukemia / 대한혈액학회지

Biphenotypic acute leukemia (BAL) is a rare type of leukemia, comprises 4% of all acute leukemias. It is more common in adults and the clinical features, as related to marrow dysfunction, are similar to those found in other patients with acute leukemia. BAL commonly shows a dimorphic blast population with, one resembling lymphoblasts and the other resembling myeloblasts. The majority of BAL patients express B-lymphoid and myeloid markers. BAL can be diagnosed by morphologic studies and by a comprehensive panel of immunological markers, as well as cytogenetic/molecular studies, such as fluorescence in situ hybridization (FISH) and reverse transcriptase-polymerase chain reaction (RT-PCR). In addition, its prognosis is relatively poor. We present here a 27 year-old female patient who showed lymphoblasts and myeloblasts on her marrow studies and these cells were positive for myeloid and B-lymphoid markers on the immunophenotypic studies. Chromosome analysis revealed 46,XX,t(6;19)(p23;p13.1),t(9;22)(q34;q11.2). A major (b3a2) type of BCR-ABL1 mRNA transcript was detected by RT-PCR, and a 5'ABL1 deletion was identified by FISH.

Acute Myeloid Leukemia with t(8;21)(q22;q22) (AML1/ETO) in a Patient with Marked Hypocellularity and Low Blasts Count / 영남의대학술지

According to the World Health Organization (WHO) classification system, cases with t(8;21)(q22;q22) should be diagnosed as acute myeloid leukemia (AML) even with a blast count of less than 20 percent in blood or bone marrow. It is an uncommon manifestation, moreover hypocellularity is rarely observed in this subtype of leukemia. Here, we report a case of t(8;21) in a patient with marked hypocellularity of less than 5 percent and a blast count of less than 20 percent. This patient responded relatively well to chemotherapy. An allogeneic bone marrow transplantation was performed with good engraftment . This case suggests that hypocellular AML with a t(8;21) has as good a prognosis as hypercellular AML with t(8;21).

A Case of Acute Lymphoblastic Leukemia with ider(9)(q10)t(9;22)(q34;q11.2) / 대한진단검사의학회지

ider(9)(q10)t(9;22)(q34;q11.2) is an isochromosome for the long arm of a derivative chromosome 9 generated by a t(9;22), resulting from the deletion of the short arm of chromosome 9. It is known to be rarely observed in acute lymphoblastic leukemia (ALL) or lymphoblastic crisis transformed from chronic myelogenous leukemia. We herein describe a 26-year-old female patient with precursor B-cell ALL, cytogenetically characterized by ider(9)(q10)t(9;22). Fluorescence in situ hybridization analysis showed two ABL-BCR fusion signals on the derivative chromosome 9 and one BCR-ABL fusion signal on the derivative chromosome 22. Although a t(9;22) and a deletion of the short arm of chromosome 9 are known to be associated with a poor prognostic factor in acute lymphoblastic leukemia, a larger study is needed to determine the prognosis of ider(9)(q10)t(9;22) cases.

Chronic Myelogenous Leukemia with a Variant Philadelphia Translocation: t(11;22)(q25;q11.2) / 대한진단검사의학회지

We report a case of chronic myelogenous leukemia displaying a variant Philadelphia translocation t(11;22)(q25;q11.2). Breakpoint 11q25 has not previously been reported. Reverse transcriptase polymerase chain reaction and fluorescence in-situ hybridization demonstrated the BCR/ABL rearrangement.

The Cytogenetic Analysis of Leukemia Patients; A Study of 515 Cases / 대한혈액학회지

BACKGROUND: Cytogenetic study is important in prediction of prognosis and evaluation of treatment effect in leukemia. The cytogenetic aberrations of leukemia are nonrandom, but uneven geographic distribution of specific abnormalities have been reported in a few studies. So we analyzed cytogenetic study to find these uneven distribution patterns. METHODS: The conventional cytogenetic study was performed for 515 cases with acute and chronic leukemia on initial diagnosis. The results were analysed in each subtypes classified according to FAB criteria. RESULTS: The aberration rate was 62.0% in acute myelogenous leukemia (AML), 72.0% in acute lymphoblastic leukemia (ALL), 92.8% in chronic myelogenous leukemia (CML), 37.5% in chronic lymphocytic leukemia (CLL), 56.9% in myelodysplastic syndrome (MDS) and 36.4% in acute undetermined leukemia. The frequent anomalies were t(8;21)(q22;q22), t(15;17)(q22;q11), -Y, +8, +21 in AML, t(9;22)(q34;q11), del(6q), +8, t(1;19)(q23;p13), +21, -20 in ALL, -7/del(7q), +8, del(12p), +11 in MDS. Philadelphia chromosome was found in 94.8% of CML and +22q-, +8 was frequent secondary changes. The incidence of t(8;21)(q22;q22) in M2, t(15;17)(q22;q11) in M3, t(9;22)(q34;q11) in ALL and -5/del5q, -7/del7q in MDS were 54.9%, 95.2%, 23.6%, 4.0% and 40.0%, respectively. CONCLUSION: There were no marked differences in distribution pattern of common aberrations compared to previous reports. But the frequency of some anomalies showed specific findings. The incidence of t(8;21) in M2 subtype and t(9;22)(q34;q11) in ALL were higher in oriental countries including our results than in western countries. The incidence of -5/del(5q) in MDS was lower in oriental countries. These findings suggest the geographic heterogeneity which may give some help to investigate the genetic and environmental influence on the karyology of tumors.

A Case of Acute Megakaryoblastic Leukemia Diagnosed by t(1;22)(p13;q13) / 대한진단검사의학회지

A four-year-old female initially presented with fever, cough, headache and bone pain. On admission, a complete blood cell count revealed anemia (Hb 8.4 g/dL, WBC 4, 630/microL, platelets 132, 000/microL) and a few blasts were observed in a peripheral blood smear. A bone marrow study revealed inadequate aspirate due to dry tap and extensive fibrosis on the biopsy section. Cytogenetic analysis showed a karyotype with 48, XX, t(1;22)(p13;q13), +der(1) t(1;22), +2. Considering the specificity of cytogenetic results and extensive myelofibrosis, acute megakaryoblastic leukemia was diagnosed. Acute megakaryoblastic leukemia with t(1;22)(p13;q13) is known to be a relatively clear-cut cytogeneticomorphological defined syndrome. Herein, we report a first case of acute megakaryoblastic leukemia with t(1;22)(p13;q13) in Korea.

Two Cases of Erythroleukemic Blast Crisis in Chronic Myelogenous Leukemia / 대한임상병리학회지

The erythroleukemic blast crisis in chronic myelogenous leukemia (CML) is rarely reported. We present two cases of erythroleukemic blast crisis of CML. In both cases, they had been treated with interferon and hydroxyurea prior to a blast crisis of CML. On blastic transformation, one patient underwent an acute clinical transformation marked with fever and hematochezia but the other showed no clinical deterioration. The blasts appeared in the peripheral blood. The bone marrow aspirates revealed megaloblastic erythroid hyperplasia (about 72%, 54% of all nucleated cells), increasing the number of myeloblasts (about 46%, 59% of all non-erythroid cells), and erythroblasts with a positive PAS stain. The cytogenetic studies revealed Philadelphia chromosomes with additional chromosomal abnormalities, t(3;21)(q26;q22) and the FISH studies revealed bcr-abl fusion signals in bone marrow cells. One case expired 8 months later despite of hydroxyuria therapy. The other case received allogeneic bone marrow transplantation (alloBMT) without complete remission but expired 34 weeks after alloBMT due to GVHD.