Myelodysplastic Features Research Articles

Characteristics and Outcomes of 38 Patients with Acute Myeloid Leukemia Evolving from Previous Well Characterized Myeloproliferative Disorder.

Antecedent hematological disorder (AHD) is a known adverse prognostic factor for patients with AML. AHD, however, encompasses a range of diverse hematological disorders. The characteristics and outcome of AML evolving from myeloproliferative disorders (MPD) without features of dysplasia remain poorly defined. Between 08/73 and 01/06, 76 patients were treated at the MD Anderson Cancer Center for AML evolving from a previous MPD. Of these, 38 were excluded from further analyses: inadequate pathological information for confident diagnosis of MPD (n=15), concomitant myelodysplastic features (n=11), chronic myelomonocytic leukemia (n=4), and less than twelve months between MPD diagnosis and AML occurrence (n=8). Baseline characteristics of remaining 38 patients with well-characterized MPD: median age 51 years (range 24–70); male 61%; cytogenetics - diploid 86%, del20q 14%; splenomegaly 27%. Diagnoses by WHO classification: polycythemia vera 47%; myelofibrosis 24%; essential thrombocythemia 18%; chronic MPD unclassifiable 11%. MPD therapy: hydroxyurea in 87% (median 3 years exposure), alkylating agent in 16%, and radioactive phosphorus in 8% of patients. AML occurred a median of 111 months (range 22 – 376) after MPD diagnosis. Median age at AML diagnosis was 65 years (range 40–81); cytogenetics were poor risk (−5, −7, 11q23, or ≥3 abnormalities) in 50% and intermediate risk in others (including diploid in 28%). Median survival was 23 weeks after AML diagnosis, and was not significantly different between patients who received AML therapy and those who received supportive therapy only (p=0.33) (figure 1), or between patients with intermediate and poor risk cytogenetics (p=0.12). Twenty-four patients received standard or high-dose Ara-C based induction chemotherapy: complete response (CR) rate was 38%, but responses were short-lived with all patients relapsing within 37 weeks in the absence of stem cell transplantation. Two patients underwent non-myeloablative matched sibling stem cell transplant in first CR: one remain leukemia free at 70 weeks, and the second relapsed 22 weeks post transplant but responded to re-induction chemotherapy, and remains alive at 38 weeks. AML evolving from a previous MPD carries an adverse prognosis, with very poor results from conventional induction chemotherapy. Exploration of novel agents in this patient population as a first line therapy is warranted. [Display omitted]

Refractory anemia with ringed sideroblasts associated with marked thrombocytosis harbors JAK2 mutation and shows overlapping myeloproliferative and myelodysplastic features

Refractory anemia with ringed sideroblasts associated with marked thrombocytosis harbors JAK2 mutation and shows overlapping myeloproliferative and myelodysplastic features

Unusual skin and testicular lesions in a patient with CMML

Chronic myelomonocytic leukemia (CMML) is a clonal disorder of hematopoetic stem cells with myelodysplastic and myeloproliferative features. Skin infiltration by leukemic cells is rare in CMML. A case is presented with severe dermatological involvement and concomitant testicular infiltration. An unusual feature was the evidence that the skin was the primary site of an acute leukemic transformation.

SALL4, a Novel Oncogene Induces Myelodysplastic Syndrome and Acute Myeloid Leukemia Via Wnt/β-Catenin Pathway.

SALL4, a gene homologous to the Drosophila homeotic spalt, is a zinc finger transcriptional factor essential for human development. In Drosophila, spalt is regulated by the Wnt signaling pathway, a pathway critical for hematopoietic self-renewal of stem cells. We cloned SALL4 and its isoforms (SALL4A and SALL4B). We used immunohistochemistry, to demonstrate that SALL4 was constitutively expressed in primary acute myeloid leukemia cells (French American British, FAB: M1 to M5, N=81). The SALL4 in RNA was quantitative in bone marrow cells derived from acute myeloid leukemia (AML) and compared to non-neoplastic hematopietic cells from a purified CD34 progenitor pool, normal bone marrow and peripheral blood by RT-PCR. SALL4 expression was present in the purified normal CD34+ cells, AML blasts, but absent in mature myeloid cells. We tested the leukemogenic potential of constitutive overexpression of SALL4 in a murine hematopoietic model. All transgenic mice overexpressing SALL4B using the CMV promoter developed hematopoietic disorders, including myelodysplastic (MDS)-like symptoms and an AML transformation that disseminated to peripheral tissues including the spleen, liver, kidney and lymph nodes. The myelodysplastic features in these transgenic mice were pathologically similar to human MDSs and manifested as ineffective myelopoiesis. Dysplatic features such as Pseudo-Pelger-Huet like atypical white cells, and increased immature cells were detectable in the transgenic mouse peripheral blood. A high level of apoptosis and increased immature cells were also evident in transgenic mouse marrows and day-7 colony-forming unit assays in vitro. Both SALL4A and SALL4B were able to bind to β-catenin in vitro and synergistically enhanced the Wnt/β-catenin signaling pathway in a reporter gene assay. Our data suggests that the constitutive expression of SALL4 is causal to the leukemic phenotype. Our model should provide a useful platform to analyze the interaction of SALL4 with Wnt/β-catenin pathway in leukemia stem cells.

Severe and prolonged myeloid haematopoietic toxicity with myelodysplastic features following alemtuzumab therapy in patients with peripheral T‐cell lymphoproliferative disorders

Alemtuzumab is effective therapy for B- and T-cell lymphoproliferative disorders (LPD) but is associated with prolonged lymphopenia. Myeloid haematological toxicities are less well described, especially in T-cell disorders, and are usually transient. We report myeloid toxicities in a phase II trial of alemtuzumab for T-cell LPD. Five of 11 patients treated developed severe neutropenia and thrombocytopenia. Three cases had prolonged cytopenias (32-88+ weeks), including two with severe marrow hypoplasia. We observed three incidences of trilineage morphological myelodysplasia, two with new clonal cytogenetic abnormalities. Alemtuzumab can be associated with prolonged severe multilineage cytopenias, marrow hypoplasia and myelodysplasia in T-cell LPD.

Serial Morphologic Observation of Bone Marrow in Aplastic Anemia in Children

Recent reports of myelodysplastic syndrome/acute myeloid leukemia (t-MDS/AML) developing after treatment with immunosuppressants and granulocyte colony-stimulating factor (G-CSF) has raised the question of whether previously unrecognized myelodysplastic features had been present or whether actual transformation had occurred. We undertook a multi-institutional study of 112 children with aplastic anemia diagnosed between 1976 and 1996 and then treated with immunosuppressants with or without G-CSF. In each case, bone marrow specimens were tested at study entry and every 6 months for 3 years to detect t-MDS/AML as defined by morphologic and molecular/cytogenetic criteria. As of December 2001, all eligible patients had been followed for a median of 3 years. Morphologic abnormalities were found in 17 cases. The patients in 4 of these cases had clonal cytogenetic abnormalities and received MDS diagnoses. The morphologic features of the patients with and without clonal cytogenetic abnormalities were indistinguishable. However, the mast cell content was lower in cases with cytogenetic abnormalities than in cases without them. An elucidation of the role of mast cells may provide information about the differences between aplastic anemia and MDS or about the transition of aplastic anemia to MDS.

Stem cell transplantation for aplastic anemia and myelodysplastic syndrome

Stem cell transplantation (SCT) from a histocompatible sibling is treatment of choice for severe aplastic anemia. Survival rates have been reported to be as high as 90% for children. Immunosuppressive therapy (IST) is employed in patients who are not candidates for SCT due to donor unavailability. The addition of cyclosporin A to antilymphocyte globulin has improved the response rate to 70-80%, and survival at 5 years among responders is about 90%. In all, 30% of patients treated by IST suffer from relapse, but long-term prognosis does not appear to be affected by this complication. Juvenile myelomonocytic leukemia (JMML) shares both myelodysplastic and myeloproliferative features. Survival (10-year) of patients with JMML without SCT is only 6%. Children with JMML should be transplanted early in the course of their disease. Conditioning regimen composed of three alkylating agents, busulfan, cyclophosphamide and melphalan has been favored by the EWOG-MDS and EBMT-Pediatric WP in the second half of the 1990s. SCT using this conditioning regimen is capable of curing approximately 50% of patients with JMML. More than 70% of patients with refractory cytopenia and more than 50% of children with advanced MDS are cured of by the early performed allogeneic SCT.

NUP98 is fused to HOXA9 in a variant complex t(7;11;13;17) in a patient with AML-M2

The t(7;11)(p15;p15.4) has been reported to fuse the NUP98 gene (11p15), a component of the nuclear pore complex, with the class-1 homeobox gene HOXA9 at 7p15. This translocation has been associated with myeloid leukemias, predominantly acute myeloid leukemia (AML) M2 subtype with trilineage myelodysplastic features, and with a poor prognosis. The derived fusion protein retains the FG repeat motif of NUP98 N-terminus and the homeodomain shared by the HOX genes, acting as an oncogenic transcription factor critical for leukemogenesis. We report here a new complex t(7;11)-variant, i.e., t(7;11;13;17)(p15;p15;p?;p1?2) in a patient with AML-M2 and poor prognosis. The NUP98-HOXA9 fusion transcript was detected by RT-PCR, suggesting its role in the malignant transformation as it has been postulated for other t(7;11)-associated leukemias. No other fusion transcripts involving the NUP98 or HOXA9 genes were present, although other mechanisms involving several genes on chromosomes 13 and 17 may also be involved. To our knowledge, this is the first t(7;11) variant involving NUP98 described in hematological malignancies.

Myelodysplastic features in an infant with cystic fibrosis presenting with anaemia, oedema and failure to thrive

Myelodysplastic features in an infant with cystic fibrosis presenting with anaemia, oedema and failure to thrive

Prolonged Severe Pancytopenia and Myelodysplastic Features Following Alemtuzumab Therapy in Patients with Cutaneous T-Cell Lymphomas.

Background. Alemtuzumab is an increasingly utilized salvage therapy for refractory and/or relapsed B- and T-cell lymphoproliferative disorders with response rates of ~35%. Therapy has been associated with significant infectious and haematologic toxicity. Multilineage cytopenias are a recognised complication, but have been described mostly among patients with CLL and are transient. We report four of twelve (33%) patients treated with alemtuzumab for T-cell lymphoproliferative disorders with unexpectedly prolonged multilineage cytopenias (4 - 11+ months) including two cases of marrow aplasia and one of definitive clonal myelodysplasia.Methods. Patients received the standard alemtuzumab schedule (Eur J Haematol 71:250, 2003) of one dose of 3mg IV on d1,10mg on d3 and 30mg on d5, then 30 mg thrice weekly for 12 weeks. Cytomegalovirus (CMV) PCR was performed in all cases of fever, or pancytopenia. Haematologic toxicity was graded according to the NCI Common Toxicity Criteria.Results. 11 patients with advanced (IIB-IV) relapsed and/or refractory cutaneous T-cell lymphomas and one with T-cell PLL were treated. The median age was 55 years (range 29 – 69) and the median number of previous treatments was 4 (range 0 – 17). The median cumulative dose of alemtuzumab was 333mg (range 98–1056). Five patients (42%) experienced grade IV (<0.5 x 109/L) neutropenia and thrombocytopenia (<25 x 109/L). In 4 cases this severity of cytopenias lasted > 2 months, some never recovering before their death, or with persisting cytopenias during follow-up. The fifth patient died five weeks after starting alemtuzumab with pancytopenia and progressive disease. Four had confirmed CMV reactivation. Neutropenia occurred within 2 weeks of reactivation and in 2 patients, pancytopenia occurred before ganciclovir commenced. One patient who did not experience prolonged pancytopenia had CMV reactivation. One had evidence of chronic parvovirus P19 infection and none had evidence of haemophagocytosis.Discussion. In our series, the alemtuzumab-associated cytopenias were more prolonged than previously described. In four patients, recovery occurred well after the expected two weeks. Two had evidence of marrow aplasia, one of whom died soon after this diagnosis; the other is alive, remaining pancytopenic and transfusion dependent at 14+ weeks after treatment. A third patient was diagnosed with myelodysplasia (cytogenetics: 45X, Y(8)/46, XY (12)), never recovering normal counts, now 12 months post treatment. There was no difference in the liklihood of developing cytopenias in terms of age, sex or dose of alemtuzumab and the pancytopenia never heralded disease recurrence. The exact mechanism of alemtuzumab-associated haematologic toxicity remains elusive. While prolonged lymphopenia is expected, pancytopenia is unexpected since neither haematopoietic stem cells (CD34+) nor more mature myeloid or erythroid cells or megakaryocytes express CD52. We believe the prolonged cytopenias observed were partially a direct effect of alemtuzumab as we excluded infective causes such as parvovirus P19 in four of the five patients and haemophagocytosis in all. Whether the CMV reactivation is involved in the development of, or prolongs the duration of the cytopenias is unknown and further study into the link between CMV and alemtuzumab in the advent of cytopenias in T-cell lymphoproliferative disorders is warranted.

Unlike CML Patients, Patients with Gastrointestinal Stromal Tumors (GIST) Treated with Imatinib Do Not Develop Hematopoietic Clonal Cytogenetic Abnormalities.

Imatinib has the ability to inhibit the dysregulated kinase activities of the BCR-ABL fusion protein in CML pts as well as the mutated KIT in GIST patients and has been successfully used to treat both diseases. Several cases of chromosomal abnormalities in Ph-negative metaphases have been reported in CML patients in chronic phase during treatment with imatinib. This is different from true clonal evolution in that the additional cytogenetic abnormalities occur in Ph-negative cells. Although this has also been rarely reported in patients receiving other therapies its frequency in patients on imatinib is relatively high (up to 17% patients) and it may occur when imatinib is given upfront or after other treatment modalities.The most common abnormalities are trisomy 8 and chromosome 7 defects, often associated with myelodysplasia. The time from the beginning of treatment until their appearance is variable, ranging from 3 months to more than a year, with the largest published series reporting a median of 6 months (Cancer 2003; 98:1905). The pathogenesis and clinical significance of these findings is still unclear and an important question is whether these clones are induced or favored by the treatment itself, since imatinib is known to have several effects on important growth regulatory proteins involved in hematopoiesis. GIST patients without hematological disease and treated with imatinib offer a unique opportunity to address this question. From Aug 2001 to Aug 2003, 11 patients with GIST were treated with imatinib at our institution and 7 agreed to participate in the sutdy. Their median age was 54-y and they were on imatinib for a median of 18 months (4 to 18) at doses between 400 to 800mg daily. Complete karyotyping on metaphase spreads from peripheral blood and bone marrow aspirates were performed. PB and BM smears were examined for myelodysplastic features. A median of 19 (15 to 24) PB and 16 (13 to 22) BM metaphases were examined for each patient. No abnormal hematological clones were detected and 1 patient had a constitutional variant 46XY, (inv9)(p11;q12) on PB and BM cells. No dysplastic features were observed. These data, although based on a small number of patients suggest that in patients without hematological disease imatinib by itself does not induce hematopoietic clonal cytogenetic abnormalities.

Autoimmune Hemolytic Anemia with Myelodysplastic Features Followed by Bilateral Adrenal Non-Hodgkin Lymphoma: A Case Report and Review of the Literature

Primary adrenal lymphoma is a rare entity characterized mainly by bilateral involvement, presenting predominantly diffuse large B-cell histology, adrenal insufficiency and poor prognosis. Approximately 85 cases have been described in the literature. We report here a case of a 77-year-old man who presented with autoimmune hemolytic anemia (AIHA), which preceded the diagnosis of lymphoma by more than 2 years. An ultrasound guided biopsy revealed diffuse, large B-cell, lymphoma; subsequent staging revealed no other disease site, and the patient was considered to have primary adrenal lymphoma. The patient had adrenal insufficiency at diagnosis. He received hormonal replacement and chemotherapy, but he succumbed to his disease because of sepsis and multi-organ failure a few days post diagnosis. To our knowledge, this is the first case in the literature in which AIHA preceded bilateral adrenal lymphoma. We also provide a summary of the current data for the clinical features, diagnosis and treatment of primary adrenal lymphoma.

Cytogenetic abnormalities in myelofibrosis determined by FISH

9611 Background: An abnormal karyotype has been correlated with poor prognosis in myelofibrosis with myeloid metaplasia (MMM) in several recent studies. This may be due to an increased proliferative index in these cases. However, conventional cytogenetics is usually hampered by the difficulty of obtaining sufficient numbers of analyzable metaphases from bone marrow aspirates in MMM. This obstacle can be overcome by fluorescence in situ hybridization (FISH), which can be performed on interphase nuclei from archival material. Methods: In this study, the bone marrow of 107 patients with MMM was analyzed using FISH and chromosomal probes 7cen, 7q, 8cen, 20q, 11cen, 12p, 13q, 17cen, 17p, 21q. Cases with myelodysplastic features or a known bcr/abl translocation were excluded from analysis. The prognostic impact of individual cytogenetic lesions on survival was evaluated using multivariate analysis. Results: In univariate analysis, -7/7q- was significantly associated with inferior outcome (median survival 99 vs....

Cytogenetic abnormalities in myelofibrosis determined by FISH

9611 Background: An abnormal karyotype has been correlated with poor prognosis in myelofibrosis with myeloid metaplasia (MMM) in several recent studies. This may be due to an increased proliferative index in these cases. However, conventional cytogenetics is usually hampered by the difficulty of obtaining sufficient numbers of analyzable metaphases from bone marrow aspirates in MMM. This obstacle can be overcome by fluorescence in situ hybridization (FISH), which can be performed on interphase nuclei from archival material. Methods: In this study, the bone marrow of 107 patients with MMM was analyzed using FISH and chromosomal probes 7cen, 7q, 8cen, 20q, 11cen, 12p, 13q, 17cen, 17p, 21q. Cases with myelodysplastic features or a known bcr/abl translocation were excluded from analysis. The prognostic impact of individual cytogenetic lesions on survival was evaluated using multivariate analysis. Results: In univariate analysis, -7/7q- was significantly associated with inferior outcome (median survival 99 vs. 25 months, p<0.001). This abnormality remained significant in a multivariate analysis including all cytogenetic parameters, our own myelofibrosis prognostic index (MPI) and the LILLE prognostic score. When a cytogenetic risk indicator (CPI), based on several cytogenetic variables, was used, patients were clearly divided into two groups with a significantly distinct outcome. Conclusions: Detection of loss of 7/7q by FISH was found to be significantly associated with inferior outcome in MMM. Multivariate analysis including established prognostic factors identified deletion of 7/7q as independent prognostic factor in patients with MMM. By using cytogenetic findings only, patients can be allocated into poor and good risk groups. No significant financial relationships to disclose.

Increased microvascular network in bone marrow of HIV-positive haemophilic patients.

Angiogenesis has been associated with the pathogenesis of myelodysplastic syndromes (MDSs). However, less is known about the significance of this process in the bone marrow of HIV-positive patients with myelodysplastic features (MDF). Trephines from 22 HIV-positive haemophilic patients were immunostained for CD34 antigen, and the microvessel density (MVD) was quantitatively evaluated and compared with that of 21 biopsies from patients with primary MDS and with that of 12 control bone marrows with no evidence of marrow disease. Bone marrow MVD in HIV-positive haemophilic patients was similar to that in patients with MDS; however, both groups revealed significantly higher MVD counts than those of control bone marrows (P=0.002). Mean MVD counts of HIV-positive haemophilic patients were significantly associated with HIV RNA levels (P=0.008). In contrast, no correlation was found between MVD and clinical HIV stage or CD4 counts at the time of biopsy. These results suggest a direct involvement of HIV in the pathogenesis of MDF in HIV infection. Elucidation of the mechanisms underlying bone marrow angiogenesis in HIV-positive patients may provide further insights into the pathobiology of AIDS.

Bone marrow histopathology following cytoreductive therapy in chronic idiopathic myelofibrosis.

To analyse systematically therapy-induced lesions of haematopoiesis in chronic idiopathic myelofibrosis (IMF). A total of 759 sequential bone marrow (BM) biopsies (median interval 32 months) were performed in 261 patients with IMF. Besides a control group (symptomatic treatment), monotherapies included busulfan, hydroxyurea and interferon. In all therapy groups hypoplasia of varying degree was a frequent finding and often accompanied by a patchy distribution of haematopoiesis. Most conspicuous was gelatinous oedema showing a tendency to develop discrete reticulin fibrosis (scleroedema). Minimal to moderate maturation defects of megakaryopoiesis and erythroid precursors occurred, but overt myelodysplastic features were most prominent following hydroxyurea and busulfan therapy. Acceleration and blastic crisis were characterized by the appearance of immature and CD34+ progenitor cells. Concerning the dynamics of fibrosis, no differences were observed between controls and the various therapy groups. In 143 patients (55%) without or with little reticulin at onset, an increase in myelofibrosis was detectable that progressed to overt collagen fibrosis. Therapy-related bone marrow lesions in IMF comprise a strikingly variable spectrum that may include aplasia with scleroedema and a patchy distribution of myelodysplastic haematopoiesis associated with progressive myelofibrosis.

Hypocellular acute promyelocytic leukemia with a tetraploid clone characterized by two t(15;17)

We describe a case of hypocellular acute promyelocytic leukemia with a tetraploid clone characterized by two t(15;17). The large leukemia cells had a bizarre nuclear configuration and multiple Auer rods. A bone marrow biopsy specimen revealed a markedly hypocellular marrow (<10% cellularity) in the absence of myelofibrosis. Myelodysplastic features were not detected. Chromosome analysis of marrow cells revealed a karyotype of 92,XXYY,del(2)(q?),t(15;17)(q22;q21)×2. Interphase fluorescence in situ hybridization revealed that the marrow cells were composed of a tetraploid clone carrying double t(15;17) and normal diploid cells. The leukemia responded well to all- trans retinoic acid. We think that the tetraploidy could be caused by endoreduplication or endomitosis of the diploid clone with single t(15;17). The unique karyotype largely contributed to the cell morphology and marrow hypoplasia, while it may not have affected on the prognosis of the acute promyelocytic leukemia.

Increased angiogenesis in the bone marrow of HIV-positive patients with myelodysplasia

<h2>Summary</h2><h3>Aim</h3> Little is known about the significance of angiogenesis in the bone marrow of HIV-positive patients with myelodys-plastic features (MDF). However, this process has been associated with the pathogenesis of primary myelodysplastic syndromes (MDS). The aim of the study was to investigate angiogenesis in the bone marrow of HIV-positive patients. <h3>Methods</h3> Bone marrow biopsies from 28 HIV-positive patients were immunostained for factor VIII and the micro-vessel density (MVD) was quantitatively evaluated and compared with that of 32 biopsies from patients with primary MDS and to 18 control bone marrows from patients with no evidence of bone marrow disease. <h3>Results</h3> Bone marrow MVD in HIV-positive patients was similar to that of MDS. However, both groups revealed significantly higher MVD counts compared to those of control bone marrows (MDF vs controls <i>P</i>=0.022, MDS vs controls <i>P</i>=0.001). <h3>Conclusions</h3> Bone marrow from HIV-positive patients with MDF reveals similar microvessel counts compared to those with primary MDS, although both differ significantly from that of control bone marrow. Elucidation of the mechanisms underlying bone marrow angiogenesis in HIV-positive patients, may provide further insights into the pathobiology of AIDS and might be of value for the development of new therapeutic strategies for this disease.

Increased angiogenesis in the bone marrow of HIV-positive patients with myelodysplasia

Little is known about the significance of angiogenesis in the bone marrow of HIV-positive patients with myelodysplastic features (MDF). However, this process has been associated with the pathogenesis of primary myelodysplastic syndromes (MDS). The aim of the study was to investigate angiogenesis in the bone marrow of HIV-positive patients. Bone marrow biopsies from 28 HIV-positive patients were immunostained for factor VIII and the microvessel density (MVD) was quantitatively evaluated and compared with that of 32 biopsies from patients with primary MDS and to 18 control bone marrows from patients with no evidence of bone marrow disease. Bone marrow MVD in HIV-positive patients was similar to that of MDS. However, both groups revealed significantly higher MVD counts compared to those of control bone marrows (MDF vs controls P=0.022, MDS vs controls P=0.001). Bone marrow from HIV-positive patients with MDF reveals similar microvessel counts compared to those with primary MDS, although both differ significantly from that of control bone marrow. Elucidation of the mechanisms underlying bone marrow angiogenesis in HIV-positive patients, may provide further insights into the pathobiology of AIDS and might be of value for the development of new therapeutic strategies for this disease.

Deletion of chromosome 15 represents a rare but recurrent chromosomal abnormality in myelocytic malignancies

We report on three cases with myelocytic malignancies cytogenetically characterized by a deletion of chromosome 15 occurring as the sole cytogenetic aberration. The deletions were defined as del(15) (q12q21) (two cases) and del(15)(q11q21) (one case). Cytogenetic analysis was supplemented by fluorescence in situ hybridization (FISH) using a chromosome 15 specific whole chromosome painting probe and probes hybridizing to the UBE3A gene on 15q11~q13, the PML gene on 15q22, and the telomeric region of 15q. Hereby, an interstitial deletion of 15q including UBE3A, but not PML and the telomeric region of 15q could be demonstrated. Two of our patients were diagnosed as acute myelocytic leukemia (AML) with bone marrow dysplasia classified as AML-M6 and AML-M4, respectively, according to the French–American–British classification; the third patient suffered from a chronic myelomonocytic leukemia (CMMoL). In two cases, the aberration was found at the time of primary diagnosis, whereas the third case showed the del(15) only during relapse of leukemia. Both cases with acute leukemia did not adequately respond to intensive chemotherapeutic treatment and died 13 and 11 months, respectively, after primary diagnosis. Our findings and the data of five previously published cases with an isolated del(15) indicate that: 1) del(15) represents a rare but recurrent abnormality in myelocytic hemopathies; 2) in our cases, del(15) was interstitial and included the region 15q11~q13/ UBE3A, but not 15q22/ PML and the telomeric region of 15q as shown by FISH; 3) del(15) occurs frequently in disorders with myelodysplastic or myeloproliferative features and may therefore affect early hematopoietic progenitor cells; and 4) del(15) may occur during disease progression and is often associated with an unfavorable prognosis.