BCR/ABL p210, p190 and p230 fusion genes in 250 Mexican patients with chronic myeloid leukaemia (CML).

There are two major forms of the BCR/ABL fusion gene, involving ABL exon 2, but including different exons of BCR gene. The transcripts b2a2 or b3a2 code for a p210 protein. Another fusion gene leads to the expression of an e1a2 transcript, which codes for a p190 protein. Another, less common fusion gene is c3a2[e19a2], which encodes a p230 protein. The incidence of one or the other rearrangement in chronic myeloid leukaemia (CML) patients varies in different reported series. This study was designed to determine the frequency of coexpresion of the p210, p190 and p230 transcripts in 250 Mexican patients with CML. We performed nested and multiplex reverse transcriptase polymerase chain reaction (RT-PCR) on bone marrow samples from adult patients and found that all cases were positive for some type of BCR/ABL rearrangement. In 226 (90.4%) patients it was p210, while the remaining 9.6% showed coexpression or one of the transcripts of p190/p210/p230. In 7% of patients with p210 expression there are both isoforms (b3a2/b2a2), presumably the result of alternative splicing. The rate of coexpression of the p190/p210 transcripts was 5%, which is much lower than in other reports. This may be due to the technical factors. These patients had high platelet counts, marked splenomegaly and chromosomal abnormalities in addition to Ph'. Other types of coexpression seen were p210/p230 and p190/p210/p230, in patients with high-risk clinical factors. Our study confirms the occurrence of coexpression of different BCR/ABL transcripts, although the rate (9.6%) was much lower than has been reported in other populations. This may reflect either the sensitivity of the detection techniques used or the possibility of genetic differences between the populations studied. Coexpression may be due to alternative splicing or to phenotypic variation, with clinical courses different from classical CML.

[Laparoscopic management of gastroesophageal reflux disease. Experience with 100 cases]. / Manejo laparoscópico de la enfermedad por reflujo gastroesofágico. Experiencia en 100 casos.

OBJECTIVE: To evaluate the results of laparoscopic Nissen-Rossetti funduplication and to compare them with the results obtained in open surgery. DESIGN: Prospective, observational, longitudinal, pre and post-procedure. CENTERS: Beneficencia Española, Hospital Angeles, and Hospital Francisco Galindo Chávez, ISSSTE, in Torreón, Coahuila, Mexico. PATIENTS AND METHOD: From December 1992 to February 1999, 100 patients with surgical indications due to gastroesophageal reflux disease (GERD) prospectively underwent a laparoscopic Nissen-Rossetti procedure. A clinical and endoscopic follow up from 3 months to 9 years was performed in 87 cases. RESULTS: Symptomatic control was achieved in 98% (85/87) of the cases and remission of overall endoscopic esophagitis in 79% (69/87); excluding Barrett cases, esophagitis remission was observed in 93% (67/72) of the subjects. The following recurrences took place: two with G-II and two with G-III esophagitis, one requiring pyloroplasty due gastric stasis, and other patient with G-IV esophagitis, who has needed to continue with postoperative dilations. Of 16 cases with Barrett's esophagus, two-showed remission and one did not return control. Perioperative complications included gastric perforations (3), acute pulmonary edema during the immediate postoperative period (1), deep vein thrombosis (1), and late esophageal perforation (1). All were resolved satisfactorily. Surgical mortality was 0 in the 100 cases undergoing the procedure. Eighty-six percent of cases had a 24-h hospital stay. Early morbidity: dysphagia in 60 patients, early satiety in 91 cases, abdominal distention in 25 cases, all this symptomatology disappears during the subsequent 3 months. Persistent morbidity: flatulence in 60% of patients, difficulty for vomiting in 10% of cases. CONCLUSION: The laparoscopic procedure is as effective as the open method with the advantage of being minimally invasive.

A t(1;22)(p13;q13) in four children with acute megakaryoblastic leukemia (M7), two with Down syndrome.

We report four children with acute megakaryoblastic leukemia (AML-M7) and t(1;22)(p13;q13), two of them with Down syndrome; their ages were 7 months, and 6, 7, and 10 years. These findings differ from those reported in children with M7 and t(1;22) at the age of presentation (exclusively under 1-year-old) and in the two cases associated with Down syndrome (t[1;22],+21c) that may be due to the high heterogeneity of the chromosomal changes in children with AML. We cannot disregard ethnic difference distribution of chromosomal changes and age of presentation in Mexican children with AML.

Deficient proliferation of myeloid, erythroid, and multipotent progenitor cells in long-term marrow cultures from patients with aplastic anemia treated with immunosuppressive therapy.

By using Dexter-type long-term marrow cultures (D-LTMC), it has been shown previously that hematopoietic progenitor cells (HPC) from patients with aplastic anemia (AA) have a deficient proliferation in vitro. The studies reported to date, however, have focused exclusively on granulomonocytic progenitors and no information exists on erythroid or multipotent progenitor cells. On the other hand, in such studies, the input progenitor cell numbers were significantly below normal levels, thus suggesting that the rapid disappearance of myeloid progenitor cells from AA D-LTMC could also be due, at least in part, to their reduced number at culture onset. In the present study, we have followed the kinetics of myeloid, erythroid, and multipotent progenitors, from 24 AA patients subjected to immunosuppressive therapy (including patients that achieved complete, partial, or no remission at all), throughout a seven-week culture period. For analysis, we grouped all the patients based on their initial content of all three types of progenitors. Thus, we were able to evaluate separately the kinetics of these cells in D-LTMC from patients with normal and subnormal levels of progenitor cells. At the time of marrow sampling, most patients showed decreased levels of HPC; in fact, only 21%, 8%, and 16% of them showed normal levels of myeloid, erythroid, and multipotent progenitors, respectively. When cultured in D-LTMC, HPC from all AA patients analyzed showed a relatively fast disappearance from the cultures. Indeed, myeloid progenitors could be detected for only six weeks, whereas erythroid and multipotent progenitors disappeared from the cultures after two and one weeks of culture, respectively. In contrast, in normal marrow D-LTMC, myeloid, erythroid, and multipotent progenitors were detected for at least seven, five, and three weeks, respectively. Such a deficient proliferation was observed even in cultures of AA patients that contained normal levels of HPC at culture onset. Interestingly, no correlation was found between HPC proliferation in D-LTMC and response to treatment. Thus, the results of this study indicate the presence of a functional in vitro deficiency in the hematopoietic system of patients with AA, including those that achieved partial or complete remission after immunosuppressive treatment. Furthermore, this work suggests that such a proliferation deficiency is more pronounced in erythroid and multipotent progenitors than in their myeloid counterparts.

Cytogenetic findings in 303 Mexican patients with de novo acute myeloblastic leukemia.

In this report we show the chromosomal changes seen in a group of 303 Mexican patients with de novo Acute Myeloblastic Leukemia (AML). Two hundred forty-two patients were diagnosed and treated at two hospitals affiliated with the Instituto Mexicano del Seguro Social (IMSS). These are the Centro Medico Nacional Siglo XXI and Centro Medico La Raza Hospitals; the remaining 61 patients were diagnosed and treated at the Hospital General de Mexico (HGM). Clonal abnormalities were detected in 75.6% of the patients; this result agrees with what has been reported in other large series of AML studies. The incidence of changes per hospital was similar in patients from the IMSS hospitals (72-75%), while an increase was seen in patients from the HGM (85.2%). The chromosomal changes seen in this study in order of frequency were: t(15;17)[18.8%], t(9;22)[9.2%], miscellaneous chromosomal changes (mainly rearrangements of chromosomes 1,2,3,12y17)[8.2%], abnormalities of 16q22 [7.3%], t(8;21)[6.3%], -7/del(7q)[5.6%], t(6;9)[5.3%], and abnormalities of 11q23 [4.6%]. We reported an increase in the incidence of certain types of chromosomal changes seen in cases of AML, in comparison with reports from other countries. These differences could be due to methodological variations, although ethnic, socioeconomic and nutritional differences must not be disregarded. We support this finding when comparing distribution of changes in the population of patients seen in the IMSS hospitals with those from the HGM; the main difference lies in the socioeconomic level.

[Interferon in the eradication of the Philadelphia chromosome in chronic myeloid leukemia]. / El interferón en la erradicación del cromosoma Filadelfia de la leucemia mieloide crónica.

OBJECTIVE: To evaluate if human recombinant interferon alpha (IFN) combined with chemotherapy is able to suppress the Philadelphia chromosome clone in patients with chronic myeloid leukemia (CML). MATERIAL AND METHODS: The cytogenetic evolution in 53 patients with CML in chronic phase de novo was studied. They received one of three treatment schemes: a) induction of remission with daunorubicin, vincristine, cytosine arabinose and prednisone (DOAP) and maintenance with IFN (n = 12); b) induction with busulfan (BUS) or hydroxyurea (HYDX) and maintenance with IFN (n = 26); c) induction with DOAP and maintenance with BUS (n = 15). RESULTS: The remission was seen two to six months after the start of treatment: 10 had complete remission, six a partial one, 14 a minor remission and 23 none. The 16 with complete or partial response received treatment with IFN. None of the 15 cases maintained with BUS had complete or partial response. The proportion of cases with complete response (3/12) was slightly lower in patients treated with intensive chemotherapy (BUS/HIDX/IFN) than in those receiving conventional treatment (7/26). CONCLUSIONS: Our results showed that: a) IFN in combination with chemotherapy induced partial or complete response in 30% of our cases; and b) intensive chemotherapy combined with IFN was not superior in terms of a cytogenetic response to treatment with monodrugs (BUS/HIDX) and IFN.

[Cytogenetic study of 22 adults and 3 children with acute lymphoblastic leukemia]. / Estudio citogenético en 22 adultos y tres niños con leucemia linfoblástica aguda.

Between 1987 and 1990 cytogenetic studies of bone marrow and lymphocytes from peripheral blood from 25 patients with de novo ALL were performed. All cases had chromosomal aberrations; however in 23 patients a normal cell line was also present. The most important structural aberrations found were: t(17;19)(q11;p13), t(2;9;22)(q34;q34;11), t(1;7)(p13;q33), t(6;11)(q26;p16), t(3;4)(q24-25;q26), t(1;12)(q23;q34), t(2;18)(q15;p12), t(2;4)(q23;q35) and t(4;11)(q21;q23). These chromosome abnormalities correlate with the response to treatment and survival and improve the identification of high-risk patients. Our study shows the presence of some chromosomal abnormalities different to those reported in the literature; however the breakpoints involved seem to be the same which suggests that these critical regions may be directly involved in the pathogenesis of these disorders.