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.

Your dilemma, my identity: Unusual immunogenetic profiles of pediatric B cell acute lymphoblastic leukemia.

B-cell acute lymphoblastic leukemia (B-ALL) is characterized by CD19 expression, which is one of the most important prerequisites, along with expression of CD10, CD22 and/or CD79a. Rearrangements involving MLL gene are seen in CD10− B-ALL (pro-B cell origin) and t(9;11)(p21;q23) is most commonly reported in acute myeloid leukemia (AML), where it is known to carry very good prognosis in pediatric AMLs and rarely in acute lymphoblastic leukemia (ALL). We report a case of CD10+, CD19− pediatric ALL with rearrangements of MLL gene as a result of t(9;11)(p21;q23), thus conferring a very poor prognosis. The case emphasizes use of comprehensive panel of antibodies for fl ow cytometric immunophenotyping and cytogenetic correlation for correct diagnosis and prognostication. KEY WORDS: Acute lymphoblastic leukemia, CD19, MLL gene, t(9;11)(p21;q23)

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.

AcrySof toric intraocular lens for post-keratoplasty astigmatism.

We report a 63-year-old male who had undergone left eye optical penetrating keratoplasty for central leucomatous corneal opacity 10 years earlier. The eye had clear donor graft with residual astigmatism of –6.50 diopter cylinder (DC) at 30°. The patient underwent clear corneal phacoemulsification with implantation of +6.0 D spherical equivalent AcrySof SN60T9 intraocular lens (IOL). Postoperatively, at 10 months, the patient had distance corrected visual acuity of 20/30 with –2.00 DC at 20°. AcrySof toric IOL offers an effective treatment option for post-keratoplasty high corneal astigmatism in patients with cataract.

An unrelated Clone of 20q Deletion Following Successful Treatment of Leukemia in Patients with t(8;21), t(15;17) or t(9;22) / 임상검사와정도관리

Cases of clonal cytogenetic abnormalities in Philadelphia-negative cells during the treatment of Philadelphia-positive CML have been previously reported. However, clonal abnormalities unrelated to the original t(8;21) or t(15;17) karyotype are not common. Deletion of 20q (del(20q)) is one of the most common recurrent cytogenetic abnormalities in myeloid neoplasms. Here we describe 3 patients with t(8;21), t(15;17), or t(9;22) who developed unrelated del(20q) after successful treatment of leukemia. We retrospectively reviewed the cytogenetic results of 23 AML patients with t(8;21)(q22;q22), 28 AML patients with t(15;17)(q22;q12), and 47 CML patients with t(9;22)(q34;q11.2). We identified 3 patients with del(20q) as the only clonal aberration unrelated to the primary karyotype when they achieved complete morphologic and cytogenetic remission. The latency period between diagnosis and emergence of del(20q) was 1, 114, and 35 months for the 3 patients, respectively. There was no evidence of therapy-related MDS/AML during the follow-up period. In 1 AML patient with t(8;21), relapse occurred in a t(8;21)(q22;q22) clone and the del(20q) clones were lost. The clinical significance of del(20q) as an unrelated clonal aberration is unknown, but our study suggests that del(20q) does not cause therapy-related MDS/AML or indicate disease progression.

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.

Inherited t(9;22) as the cause of DiGeorge syndrome: a case report

DiGeorge syndrome is associated with microdeletion of chromosome 22q11.2. Most cases occur sporadically although vertical transmission has been documented. We report a rare case of DiGeorge syndrome in an 8-year-old girl. Blood sample of the patient was cultured and harvested following standard procedure. All of the 20 cells analysed showed a karyotype of 45,XX,-22,t(9;22)(p23;q11.2). Cytogenetic investigation done on the patient’s mother revealed that she was the carrier for the translocation. Her karyotype was 46,XX,t(9;22)(p23;q11.2). Fluorescence in situ hybridisation (FISH) analysis using TUPLE1 and N25 (Vysis, USA) probes showed deletion of the 22q11.2 region in the patient, confi rming the diagnosis of DiGeorge syndrome. FISH analysis showed no deletion of the region in the mother.

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

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.

Effect of the Gardenia extracts T9 on VP16 mRNA in herpes simplex virus type-1 infected mice's brains / 中华微生物学和免疫学杂志

Objective To investigate the effect of the Gardenia extracts T9 on herpes simplex virus (HSV) viral protein 16(VP16) in HSV-1 infected mice's brains and its potential anti-viral mechanism. Methods HSV-1 infection was induced in BALB/c mice, the expression of HSV VP16 was detected by RTPCR on the 4th, 7th, 10th, 14th, and 21st day. Results The expression of VP16 mRNA decreased in both groups of large and low doses compared with virus group at the same time. Conclusion Gardenia extracts T9 can down-regulate the expression of VP16 mRNA in HSV infected mice's brains, and it may be one of its anti-HSV mechanisms.

A Case of Acute Promyelocytic Leukemia with PML/RARA Translocation Showing Familial t(9;15)(q34;q22)

We report the unusual case of an APL patient with a familial t(9;15)(q34;q22) and acquired t(15;17) (q22;q21). This is unique in that the patient had a constitutional abnormality with the same breakpoints as those observed in the tumor clone from the APL. It is unclear if the breakpoint, 15q22, in the constitutional aberration influenced the induction of the PML/RARA translocation in the APL. If a specific translocation in a patient with leukemia does not go away with clinical improvement, a congenital or familial chromosomal abnormality should be considered. Additional patients with similar findings are needed to understand the pathogenesis of these events.

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.

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 Chronic Myelogenous Leukemia with ider(22)(q10)t(9;22)(q34;q11.2) as Clonal Evolution / 대한진단검사의학회지

The ider(22)(q10)t(9;22)(q34;q11.2) is a rare secondary karyotypic aberration of Philadelphia chromosome positive chronic myelogenous leukemia (Ph+ CML) and was associated with disease progression and poor clinical outcomes in most of the previously reported cases. We experienced a case of Ph+ CML with the occurrence of ider(22)(q10)t(9;22)(q34;q11.2) as clonal evolution preceding an hematologic feature of accelerated phase for 3 years. So this chromosomal abnormality was not always correlated with poor prognosis. Relevant literature was reviewed.

Holistic management of traumatic spinal cord injury resulting from a fracture of T-09 vertebra.

Traumatic spinal cord injury (SCI) is an disastrous condition resulting in not only disability and handicap to the victims but also profound psychological damage. We report a case of complete spinal cord injury resulting from a fracture of T-9 vertebra in a car accident. Emergency management is needed to prevent further damage to the neural tissue, as well as to treat a life threatening condition. Surgical treatment to maintain spinal alignment and stability provides early mobilization to prevent the complications caused by the immobilization syndrome. A holistic approach to management is fundamental to the rehabilitation program. Although physical impairment and disability are permanent, psychosocial management focused on cognitive and behavioral modification together with home modification plays an important role in reducing disability and handicap and allowing a patient to return to his home and previous social function with the best quality of life as possible.

ider (9) (q10)t (9;22) (q34;q11.2) as Secondary Karyotypic Aberration of Chronic Myelogeous Leukemia / 대한임상병리학회지

Although occasional patients with chronic myeloid leukemia (CML) have chromosomal changes other than Philadelphia chromosome early in the disease, in typical cases the 9;22 translocation remains the sole abnormality throughout the disease course in chronic phase. When disease progression occurs, however, 75-80% develop additional chromosome aberrations. These secondary changes sometimes precede the more aggressive manifestations hematologically and clinically and thus may serve as valuable prognostic indicators. ider (9) (q10)t (9;22) (q34;q11.2) is very rare and a recurrent chromosomal abnormality associated with acute lymphoblastic leukemias (ALL) and lymphoblastic crisis of CML. And ider (9) (q10)t (9;22) (q34;q11.2) is a lymphoid-specific rearrangement and the patients with this abnormality are of older age on average. They commonly show pre-B cell lineage immunophenotype and L2 morphology. We report a case of ider (9) (q10)t (9;22) (q34;q11.2) as secondary aberration in a patient with lymphoblastic crisis of CML.

ANTISPERMATOGENIC EFFECT OF MONOMER T_8 FROM TRIPTERIGIUM WlLFORDII / 中国药理学通报

A ready-made Chinese herb containing the glycosides of Tripteri-gium wilfordii ( GTW ) have been reported to cause testicular atrophy in men. Various fractions isolated from GTW were screened in experiments on rats and mice to observe their antifertility effects and found that the monomer T9 among the requirements for male contraceptive need to be elucidated. T9 was administered through gastric intubation at a dose of 0.1mg/kg?d-1 7w? All the T9 treated rats exhibited minimal testicular damage at the end of seventh week of treatment, but causes severe damages mainly the epididymal, the spermatozod showed various structural abnormalities, including cracked midpiece, decapitation of the sperm head commonly ( above 90% ) . It is no malformed round or tadpoleshapes head sperms discernible, no significant changes were seen in main visceral organs, no immunosuppressive actions was observed. The potencies of anti-sperm activity of T9 is 100 times stronger than GTW.