A new recurring chromosome 13 abnormality in two older patients with de novo acute myeloid leukemia: An Indian experience

We report here two cases of trisomy 13 in acute myeloid leukemia M1 subtype. short-term unstimulated bone marrow and peripheral blood lymphocyte culture showed 47, XY, +13 in all metaphase plates and trisomy 13 was confirmed with whole chromosome paint probes. Trisomy 13 in AML-M1 is a rare numerical abnormality. This is the first Indian report of sole trisomy 13 in AML-M1. Here, we present two cases of elder male patients, which may constitute a distinct subtype.     

The Philadelphia chromosome in acute leukemia.

The cytogenetics, cytology and cytochemistry, clinical findings, therapeutic response and survival of patients presenting with acute leukemia and the Philadelphia chromosome (Ph1) are briefly reviewed based upon a survey of the world literature and 16 cases seen at the University of Minnesota during the last 10 years. Details regarding the 16 cases from the University of Minnesota series are presented and two appendices listing the majority of reports of Ph1 + acute leukemia are included. Comparison of adults with Ph1+ and Ph1- acute leukemia demonstrate important clinical, therapeutic and prognostic differences. In general, patients with Ph1+ acute leukemia respond less well to treatment and survive significantly shorter periods of time. Since the presence of the Philadelphia chromosome in acute leukemia has therapeutic and prognostic significance, marrow chromosome studies should be performed in adults presenting with acute leukemia, especially acute lymphocytic leukemia.     

Acquired pericentric inversion of chromosome 9 in acute myeloid leukemia

Pericentric inversion of chromosome 9 involving the qh region is relatively common as a constitutional genetic aberration without any apparent phenotypic consequences. However, it has not been established as an acquired abnormality in cancer. Among the three patients reported so far in the literature with acquired inv(9), only one had acute myeloid leukemia (AML). Here we describe an unique case where both chromosomes 9 presented with an acquired pericentric inversion with breakpoints at 9p13 and 9q12 respectively, in a AML patient with aberrant CD7 and CD9 positivity. Additionally, one der(9) also showed short arm deletion at 9p21 to the centromeric region and including the p16 gene. The constitutional karyotype was normal. This is probably the first report describing an acquired inv(9) involving both chromosomes 9 in AML. The possible significance of this inversion is discussed.     

Phocomelia and additional anomalies in two sisters

Summary Two daughters of non consanguineous normal parents had phocomelia of both lower extremities with 4 toed feet. The older sister also had phocomelia of the left upper extremity with 5 finger rays; she died immediately after birth. Autopsy disclosed a congenital diaphragmatic hernia, common mesentery and agenesis of the gallbladder, and normal female genitalia. In addition, the younger sister showed a bony skull defect, diastasis recti, agenesis of the uterus and agenesis or atresia of the vagina, hypoplasia of the sacrum and hypo/dysplasia of the pelvic bones. Her growth and mental development were normal. The patterns of anomalies of the two sisters do not fit into any of the syndromes featuring phocomelia; there was no prenatal exposure to thalidomide or any other possible teratogen.Dedicated to Professor W. Lenz on the occasion of his 70th birthday     

Cytogenetic studies in 30 patients with Burkitt's lymphoma or L3 acute lymphoblastic leukemia with special reference to additional chromosome abnormalities

We performed cytogenetic analysis in 23 consecutive patients with Burkitt's ALL and 7 patients with Burkitt's lymphoma. Only one patient had a normal karyotype. Twenty-seven patients had a (8;14) translocation and 2 a (2;8) translocation. No (8;22) translocation was seen. In 12 patients (41%), the t(8;14) was the only chromosome rearrangement whereas in the 18 remaining cases (59%), the t(8;14) or t(2;8) was associated with other numerical or structural abnormalities. Chromosomes 1, 7 and 6 were rearranged in 10, 8, and 5 patients, respectively, usually in translocations, duplications, deletions (chromosome 6), or isochromosome of the long arm (chromosomes 1 or 7). The incidence of these additional rearrangements is discussed with regard to previously published reports and the chromosome localization of oncogenes.     

Cytogenetic analysis in 139 Tunisian patients with de novo acute myeloid leukemia

This paper presents the results of a cytogenetic analysis in 139 Tunisian patients with de novo acute myeloid leukemia (AML), including 27 children aged 1-15 years and 112 adults. Mean age was 32 (range 1-75) and the M/F ratio was 1.43. Of our patients, 45% had apparently normal karyotypes. Acquired chromosome aberrations were found in 77 (55% ) patients. t(8;21) was identified in 27 patients (19%); t(15;17) in 13 patients (9%); deletion 7q or monosomy 7 in seven patients (5%); +8 in seven patients (5%); abnormal 16 in four patients (3%); 11q23 rearrangements in two patients (2%) and del(5q), in one patient (1%). The remaining 16 patients had miscellaneous clonal abnormalities. Specific translocations associated with the FAB type were found: t(8;21) with AML2 and t(15;17) with AML3. We concluded that our study in a Tunisian population confirmed the relation between some specific abnormalities and the FAB classification. We found a higher incidence for t(8;21) than usually described.     

Complex chromosome 17p rearrangements associated with low-copy repeats in two patients with congenital anomalies

Recent molecular cytogenetic data have shown that the constitution of complex chromosome rearrangements (CCRs) may be more complicated than previously thought. The complicated nature of these rearrangements challenges the accurate delineation of the chromosomal breakpoints and mechanisms involved. Here, we report a molecular cytogenetic analysis of two patients with congenital anomalies and unbalanced de novo CCRs involving chromosome 17p using high-resolution array-based comparative genomic hybridization (array CGH) and fluorescent in situ hybridization (FISH). In the first patient, a 4-month-old boy with developmental delay, hypotonia, growth retardation, coronal synostosis, mild hypertelorism, and bilateral club feet, we found a duplication of the Charcot-Marie–Tooth disease type 1A and Smith-Magenis syndrome (SMS) chromosome regions, inverted insertion of the Miller-Dieker lissencephaly syndrome region into the SMS region, and two microdeletions including a terminal deletion of 17p. The latter, together with a duplication of 21q22.3-qter detected by array CGH, are likely the unbalanced product of a translocation t(17;21)(p13.3;q22.3). In the second patient, an 8-year-old girl with mental retardation, short stature, microcephaly and mild dysmorphic features, we identified four submicroscopic interspersed 17p duplications. All 17 breakpoints were examined in detail by FISH analysis. We found that four of the breakpoints mapped within known low-copy repeats (LCRs), including LCR17pA, middle SMS-REP/LCR17pB block, and LCR17pC. Our findings suggest that the LCR burden in proximal 17p may have stimulated the formation of these CCRs and, thus, that genome architectural features such as LCRs may have been instrumental in the generation of these CCRs.     

Leptotrichia buccalis bacteremia in two patients with acute myelogenous leukemia

Leptotrichia buccalis is rarely implicated in systemic disease. We report two patients with clinically significant L. buccalis bacteremia which developed during the neutropenia secondary to chemotherapy. Based upon our experience, L. buccalis bacteremia should be considered in certain high-risk immunocompromised patients with mucositis and/or gingivitis.     

Acute lymphocytic and myelomonocytic leukemia associated with low platelet counts and a 21q- marker chromosome

Summary A terminal deletion of the long arm of one chromosome 21 at band q21 was found in two patients with acute leukemia and a low platelet count: one case of acute myelomonocytic leukemia and one case of acute lymphocytic leukemia. The segment deleted from chromosome 21 could not be found translocated to any other chromosome of the complement. The results indicate that the 21q- marker chromosome may be due to a true deletion and that the marker is not specific for primary thrombocythemia or other myeloproliferative disorders associated with thrombocytosis.     

Prognostic significance of chromosome analysis in de novo acute myeloid leukemia (AML)

Between 1981 and 1986 cytogenetic studies of bone marrow and/or blood cells in 139 patients with de novo acute myeloid leukemia (AML) were performed. The overall incidence of chromosomal aberrations was 53%, and this was not significantly influenced by sex, age nor the FAB classification. The aberrations most often found were: complex anomalies (n = 13), t(8; 21) (n = 10), trisomy 8 (n = 9), monosomy 7 (n = 6), monosomy 5, 5q-, trisomy 11, 12p- (n = 4) and trisomy 6, 11q-, inv (n = 3). The prognostic significance of chromosomal findings was evaluated in 112 patients treated by combination chemotherapy. The chromosomal status NN, AN, AA did neither significantly influence complete remission rate (NN: 68%, AN: 71%, AA: 60%) nor mean survival (NN: 24, AN: 26.6, AA: 35.6 months). On the other hand, certain types of chromosomal anomalies were of prognostic value. CR was obtained in all 10 patients with t(8; 21) but only in 2 out of 9 patients with complex aberrations. Median duration of CR in patients with t(8; 21) was significantly longer than in patients with a normal karyotype (30 vs 7 months).     

The interaction of daunorubicin and mitoxantrone with the red blood cells of acute myeloid leukemia patients

The effect of DNR and MIT on erythrocyte membrane structure was examined using Electron Spin Resonance spectroscopy and the fluorimetric technique. The results suggest that the in vivo interaction of the drugs with the RBCs of AML patients led to a perturbation in the structure of plasma membrane components. Differences between DNR and MIT were only noted in the interaction of the drugs with deeper regions of the lipid bilayer     

The origin and evolution of mutations in acute myeloid leukemia

Most mutations in cancer genomes are thought to be acquired after the initiating event, which may cause genomic instability and drive clonal evolution. However, for acute myeloid leukemia (AML), normal karyotypes are common, and genomic instability is unusual. To better understand clonal evolution in AML, we sequenced the genomes of M3-AML samples with a known initiating event (PML-RARA) versus the genomes of normal karyotype M1-AML samples and the exomes of hematopoietic stem/progenitor cells (HSPCs) from healthy people. Collectively, the data suggest that most of the mutations found in AML genomes are actually random events that occurred in HSPCs before they acquired the initiating mutation; the mutational history of that cell is "captured" as the clone expands. In many cases, only one or two additional, cooperating mutations are needed to generate the malignant founding clone. Cells from the founding clone can acquire additional cooperating mutations, yielding subclones that can contribute to disease progression and/or relapse.     

Annular promyelocytes in acute myeloid leukemia

Granulocytes with ring-shaped nuclei (annular granulocytes; ring granulocytes) are normal bone marrow constituents in rodents. Studies in man have shown a small number of these cells in cases of myeloproliferative diseases. Myelocytes and metamyelocytes have also been described. Similar to rodents and some other animal species, the annular promyelocyte also exists in humans. The significance of these very rare cells in human haemopoiesis becomes an interesting question.     

Interleukin-17 in acute myeloid leukemia

There are several reports that angiogenesis plays important roles in hematological malignancies including acute myeloid leukemia (AML). Human interleukin-17 (IL-17) is a proinflammatory cytokine produced by activated CD4 T cells. IL-17 plays a potential role in T cell mediated angiogenesis. The role of IL-17 in pathologic angiogenesis has not been evaluated yet. The aim of the study was to determine plasma level of IL-17 in patients with AML. IL-17 levels were measured by ELISA in plasma samples taken from 68 adult patients with AML before chemotherapy was administered. In addition 20 out of 68 patients were reanalysed after achieving complete remission (CR). Ten samples from healthy volunteers were evaluated as the control. In this study we have demonstrated that serum level of IL-17 is not elevated in AML patients. These results suggest that angiogenesis in AML is not mediated by CD4 T cells. To our knowledge this is the first report about IL-17 serum level in acute leukemias. We are currently evaluating IL-17 levels in others haematological malignancies.