1/8. Triple philadelphia chromosomes with major-bcr rearrangement in hypotriploid erythroleukaemia.The philadelphia (Ph) chromosome is observed in approximately 1% of patients with acute myeloblastic leukaemia (AML), especially subtypes M1 and M2 in the French-American-British classification. We describe here a cytogenetic and molecular investigation of a rare case with Ph-positive AML M6 (erythroleukaemia). A 63-yr-old woman was diagnosed as having erythroleukaemia. Leukaemic cells were positive for CD4 and CD7 as well as CD13, CD33, CD34 and HLA-DR. They were analyzed by G-banding, fluorescence in situ hybridization (FISH), Southern blot and reverse transcriptase polymerase chain reaction analyses. The karyotypes at diagnosis were as follows: 61, XX, -X, -1, -2, -3, -4, -5, -7, t(9;22)(q34;q11)x 2, -15, -16, -17, -18, 19, 21, 22 [3]/61, idem, -22, der(22)t(9;22) [36]. FISH with BCR/ABL probes showed that 39% and 57% of interphase nuclei had double and triple BCR/ABL fusion signals, respectively. Chromosome analysis in complete remission showed a normal karyotype in all 20 metaphases, confirming the diagnosis as Ph positive-acute leukaemia. FISH at relapse showed that 92% of interphase nuclei had triple fusion signals. Rearrangement of major breakpoint cluster region (M-bcr) in the BCR gene and coexpression of p210-type (b2a2) and p190-type (e1a2) BCR/ABL fusion transcripts due to alternative splicing were also detected. We conclude that clonal evolution from double to triple Ph chromosomes may be implicated in the disease progression. Considering other two reported cases, Ph-positive erythroleukaemia appears to be correlated with coexpression of myeloid/T-lymphoid markers and hyperdiploidy with double or triple Ph chromosomes, although breakpoints in the BCR gene are heterogenous.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/8. Cross-species color banding in ten cases of myeloid malignancies with complex karyotypes.Cross-species color banding is a multiple-color fluorescence in situ hybridization (FISH) technique using probes developed from other animal species. Hybridization to human metaphases produces color banding patterns specific for each homologous chromosome pair. The technique has been evaluated in a complementary manner with G-banding and chromosome painting in a series of 10 myeloid malignancies with complex or unresolved karyotypes. color banding detected the majority of chromosomal abnormalities, which had been identified by G-banding and in each case revealed chromosomal changes that G-banding had not identified. Painting was necessary to confirm these abnormalities due to the limitation of only seven colors in the color-banded karyotype. At the same time, painting fortuitously uncovered cryptic abnormalities in 6 of 10 cases that had not been detected by color banding. Insertions were visible by painting only. This study has demonstrated that in the analysis of complex karyotypes, the application of color banding revealed the involvement of the long arm of chromosome 3, indicating a poor risk, in two cases not identified by G-banding. Therefore, these techniques applied together have revealed cryptic chromosomal abnormalities with prognostic significance, which in some cases may have implications for patient management.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
3/8. Acute myeloblastic leukaemias of FAB types M6 and M4, with cryptic PML/RARalpha fusion gene formation, relapsing as acute promyelocytic leukaemia M3.Demonstration of either the translocation t(15;17)(q22;q21) or the fusion of PML and RARalpha genes is regarded as diagnostic for acute myeloid leukaemia (AML) of FAB type M3, but has occasionally been seen in other FAB types. We present two such cases. Case 1 presented with FAB type M6 and a complex karyotype involving chromosomes 1, 2, 11 and 17. Bone marrow relapse of FAB type M3 followed autologous bone marrow transplantation. Subsequent marrow dysplasia and an M6 relapse were accompanied by a new cytogenetic clone involving chromosomes X, 2, 4, 6, 7 and 16. fluorescence in situ hybridization (FISH) of metaphase chromosomes at diagnosis showed insertion of material from chromosome 17 into a 'normal' 15 with juxtaposition of PML and RARalpha. Case 2 presented as AML M4 and relapsed as M3. cytogenetic analysis at diagnosis and in relapse showed 46,XY,t(15;17)(q22;q11),del(16)(q22). FISH analysis showed this to be a three-way translocation involving chromosomes 15, 16 and 17 again with juxtaposition of PML and RARalpha. reverse transcription-polymerase chain reaction (RT-PCR) revealed PML/RARalpha fusion at diagnosis, in remission and in first relapse. These examples strengthen the case for RT-PCR screening of all AML patients for these fusion genes.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
4/8. Isolated pentasomy of chromosome 8 in erythroleukemia.Pentasomy 8 as a sole anomaly in hematological disorders is rare. Only 2 such cases, one in acute monocytic leukemia and one in chronic myelomonocytic leukemia have been described in the literature to date. Here, we report the first case of a 42 year old man with erythroleukemia displaying a pentasomy 8 clone. Conventional cytogenetics of bone marrow cells showed 16 metaphases with pentasomy 8 and 9 with normal diploidy. fluorescence in situ hybridization (FISH) analysis using a whole chromosome painting probe and a centromeric probe specific for chromosome 8 confirmed the presence of pentasomy 8 and also revealed a low percentage of a trisomic and a tetrasomic clone. The patient died three days after diagnosis without chemotherapy. The findings suggest that pentasomy 8 is associated with a heterogeneous group of myeloid disorders and probably plays a specific role in the progression of myeloid neoplasia.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
5/8. Congenital anerythremic erythroleukemia presenting as hepatic failure.We report an atypical case of congenital erythroleukemia in a child born with hepatosplenomegaly and abnormal liver tests. The initial peripheral blood cell count showed anemia and hyperleukocytosis with erythroblastosis that disappeared 1 week later. During the next 5 weeks, no blasts were found in the blood, and less than 5% were found on 2 successive bone marrow aspirates. The infant died of hepatic failure. The suspected diagnosis on a premortem liver biopsy was confirmed by an autopsy that showed a blastic infiltration in many organs. These cells expressed only erythroid markers glycophorin A and C. Rearrangement of the myeloid lymphoid leukemia gene was not found by fluorescence in situ hybridization. The main differential diagnoses include metabolic diseases, Langerhans histiocytosis, Pepper syndrome, transient myeloproliferative disorder, and leukemoid reactions. Although some of these can be excluded by the pathologist, others require a multidisciplinary confrontation: clinical, biologic, genetic, and pathologic examinations.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
6/8. Identification of pericentric inversion 12, inv(12)(p13.1q11), by fluorescence in situ hybridization in a patient with acute myeloid leukemia (AML-M6).Using probes located between 12p12.1 and 12p13.3, we performed fluorescence in situ hybridization (FISH) analysis and identified an inv(12)(p13.1q11) in a patient with acute myeloid leukemia (AML-M6). Standard cytogenetic analysis had identified the rearranged chromosomes 12 as del(12) (p11p13). Although deletions and translocations involving band 12p13 are fairly common chromosomal abnormalities observed in a broad spectrum of hematologic malignancies, inv(12) is a rather rare abnormality. We compare the clinical and cytogenetic findings with those of the previous cases reported in the literature.- - - - - - - - - - ranking = 5keywords = hybridization (Clic here for more details about this article) |
7/8. Translocation (3;5)(q21;q34) in erythroleukemia: a molecular and in situ hybridization study.Translocation (3;5) is an uncommon karyotypic aberration in acute myeloid leukemia (AML). With the exception of M3, t(3;5) has been reported in every other subtype of AML, being most frequently associated with AML M6. Although a variety of breakpoints have been described, it has been suggested that the breakpoints in t(3;5) of all the reported cases should be assigned to 3q25.1 and 5q34. Recently, the breakpoints in three pediatric cases of AML M2 with t(3;5) were cloned and shown to involve the myelodysplasia/myeloid leukemia factor I (MLF1) gene on 3q25.1 and the nucleophosmin (NPM) gene on 5q34, generating a chimeric NPM/MLF1 transcript. An adult case of indolent erythroleukemia was found on karyotypic analysis to have t(3;5)(q21;q34). In about 60% of cells, the translocation was unbalanced, resulting in loss of the der(3) chromosome, implying that the critical leukemogenic sequence might reside on the der(5) chromosome. Molecular analysis of this case, however, failed to show rearrangement of the NPM gene and an MLF1/NPM transcript. A review of other reported cases of AML M6 with t(3;5) showed that the commonest breakpoint on chromosome 3 was also assigned to 3q21, as in our case. The considerable clinical, pathologic, cytogenetic and molecular differences observed in AML with t(3;5) suggest that these cases might be heterogeneous.- - - - - - - - - - ranking = 4keywords = hybridization (Clic here for more details about this article) |
8/8. Abnormal erythropoiesis in erythroleukemia: a fluorescence in situ hybridization study.Erythroleukemia is an uncommon leukemia with heterogeneous morphologic and karyotypic features. Some cases might actually represent acute myeloid leukemia with a reactive erythroid hyperplasia. In this report, we described a 68-year-old woman with erythroleukemia and monosomy 7 and showed by fluorescence in situ hybridization that both myeloid and erythroid lineage were clonally involved and that both normal and abnormal erythroid populations coexisted, albeit indistinguishable by morphological examination. These findings may account for the variation in the erythropoietic activity observed in the clinical course of erythroleukemia.- - - - - - - - - - ranking = 5keywords = hybridization (Clic here for more details about this article) |