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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report two cases of Philadelphia chromosome (Ph)-positive acute leukemia with definite myeloid markers. Ph was the sole chromosomal abnormality at presentation, and neither eosinophilia, basophilia, thrombocytosis nor hepatosplenomegaly was present. In both cases, Ph+ myeloblasts showed positive stain for myeloperoxidase and naphthol ASD chloroacetate esterase, which fulfilled the FAB criteria of acute myelogenous leukemia (AML). Ph+ myeloblasts co-expressed myeloid and B-lymphoid antigens (CD10, CD13, CD19 and CD33). In case 1, myeloblasts rearranged M-BCR, and the expression of M-BCR/ABL chimeric RNA was demonstrated by using the reverse transcription polymerase chain reaction (RT-PCR). They also clonally rearranged IGH. Ph clone disappeared on cytogenetic analysis in remission, and granulocytes in remission did not have rearranged M-BCR. In case 2, morphocytochemically distinct myeloid and lymphoid blast populations were seen. Myeloblasts and lymphoblasts were enriched > 96% as CD19-/CD33+ and CD19+/CD33- populations, respectively. Both of them possessed the identical rearrangement of IGH and M-BCR, indicating a common leukemic progenitor cell origin. Furthermore, m-BCR/ABL was detected in addition to M-BCR/ABL on RT-PCR. Accordingly, both cases were diagnosed as de novo Ph+ acute leukemia rather than as chronic myelogenous leukemia in blastic crisis. Their mixed B-lymphoid/myeloid characteristics strongly suggest that so-called 'Ph+ AML' is derived from Ph+ myeloid/B-lymphoid stem cells.
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PMID:B-lymphoid/myeloid stem cell origin in Ph-positive acute leukemia with myeloid markers. 832 35

We have shown that the incidence of complex translocations is approximately the same in chronic myeloid leukemia, characterized by the t(9;22)(q34;q11), and in acute myeloid leukemias, characterized by the t(15;17)(q22;q11) or t(8;21)(q22;q22). This incidence is almost threefold greater than the incidence of complex translocations in lymphomas and lymphoid leukemias characterized by the t(8;14)(q24;q32) or t(14;18)(q32;q21). The genomic recombination, which gives rise to the translocations in lymphoid cells, results mostly from errors of IGH gene rearrangement. Genomic recombination underlying myeloid leukemias has a different cause, and a clue to this may lie in the greater incidence of complex chromosome rearrangements.
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PMID:A greater incidence of complex translocations in myeloid leukemias than in lymphomas and lymphoid leukemias associated with IGH rearrangement. 861 94

Stem cells of acute myeloid leukemia (AML) have been identified as immunodeficient mouse-repopulating cells with a Lin(-)CD34(+)38(-) phenotype similar to normal hematopoietic stem cells. To identify the leukemia-propagating stem cell fraction of Philadelphia chromosome-positive (Ph(+)) leukemia, we serially transplanted human leukemia cells from patients with chronic myeloid leukemia blast crisis (n = 3) or Ph(+) acute lymphoblastic leukemia (n = 3) into NOD/SCID/IL-2Rgammac(-/-) mice. Engrafted cells were almost identical to the original leukemia cells as to phenotypes, IGH rearrangements, and karyotypes. CD34(+)CD38(-)CD19(+), CD34(+)38(+)CD19(+), and CD34(-)CD38(+)CD19(+) fractions could self-renew and transfer the leukemia, whereas the CD34(-)CD38(+)CD19(+) fraction did not stably propagate in NOD/SCID mice. These findings suggest that leukemia-repopulating cells in transformed Ph(+) leukemia are included in a lineage-committed but multilayered fraction, and that CD34(+) leukemia cells potentially emerge from CD34(-) populations.
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PMID:Irrespective of CD34 expression, lineage-committed cell fraction reconstitutes and re-establishes transformed Philadelphia chromosome-positive leukemia in NOD/SCID/IL-2Rgammac-/- mice. 2002 84

Reprogramming blood cells to induced pluripotent stem cells (iPSCs) provides a novel tool for modeling blood diseases in vitro. However, the well-known limitations of current reprogramming technologies include low efficiency, slow kinetics, and transgene integration and residual expression. In the present study, we have demonstrated that iPSCs free of transgene and vector sequences could be generated from human BM and CB mononuclear cells using non-integrating episomal vectors. The reprogramming described here is up to 100 times more efficient, occurs 1-3 weeks faster compared with the reprogramming of fibroblasts, and does not require isolation of progenitors or multiple rounds of transfection. Blood-derived iPSC lines lacked rearrangements of IGH and TCR, indicating that their origin is non-B- or non-T-lymphoid cells. When cocultured on OP9, blood-derived iPSCs could be differentiated back to the blood cells, albeit with lower efficiency compared to fibroblast-derived iPSCs. We also generated transgene-free iPSCs from the BM of a patient with chronic myeloid leukemia (CML). CML iPSCs showed a unique complex chromosomal translocation identified in marrow sample while displaying typical embryonic stem cell phenotype and pluripotent differentiation potential. This approach provides an opportunity to explore banked normal and diseased CB and BM samples without the limitations associated with virus-based methods.
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PMID:Efficient generation of transgene-free induced pluripotent stem cells from normal and neoplastic bone marrow and cord blood mononuclear cells. 2129 96

The t(11;14)(q13;q32) involving IGH and CCND1 a nd t(9;22) (q34;q11.2) involving BCR and ABL1 are common abnormalities in plasma cell myeloma (PCM) and chronic myelogenous leukemia (CML), respectively. However, the concurrence of the two malignancies is extremely rare. Herein, we present a case of an 87-year-old male who presented with anemia and monocytosis. FISH studies on a bone marrow sample enriched for plasma cells detected a t(11;14) positive for IGH and CCND1 fusion in 92% of nuclei. However, cytogenetic analysis of the bone marrow revealed a t(9;22)(q34;q11.2) in 40% of the metaphases. Interphase and metaphase FISH studies on the sample confirmed the presence of the BCR-ABL1 fusion in 88% of nuclei but did not show any signals corresponding to the derivative 9, suggesting a variant t(9;22) with a deletion or additional material of unknown origin at the 9q34 band of the derivative 9 and a derivative 22 bearing the BCR-ABL1 fusion gene. The concurrence of plasma cell myeloma and chronic myelogenous leukemia is extremely rare with less than 20 cases reported. The molecular pathway in which the multiple malignancies arise is still poorly understood, and this case provides insight into the concurrence of PCM and CML.
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PMID:An Adult Male Presenting with Concurrent Plasma Cell Myeloma Involving a CCND1-IGH Translocation and Chronic Myelogenous Leukemia with a Variant (9;22) Translocation. 2758 82

Approximately 5-10% of chronic myeloid leukemia (CML) patients are found to have structural or numerical additional chromosomal abnormality (ACAs) in addition to the characteristic t(9;22)(q34;q11.2) BCR/ABL1 at the time of diagnosis. The prognostic significance of such additional chromosomal abnormalities has been controversial. Translocation t(11;14)(q13;q32) CCND1-IGH is typically associated with mantle cell lymphoma or a subset of plasma cell myeloma and is exceedingly rare in myeloid neoplasm. Here we report a unique case describing a patient found at diagnosis of chronic phase CML to have both the Philadelphia chromosome as well as t(11;14)-a rare cytogenetic combination. The patient was treated with imatinib with appropriate hematologic response but persistent disease by FISH and RT-PCR. She was switched to dasatinib and eventually achieved cytogenetic remission in both translocations, but still with persistent RT-PCR evidence of BCR-ABL1 fusion. As cyclin D1 is a regulatory subunit of cyclin-dependent kinases CDK4 and CDK6 and is required for the cells to progress through the G1 phase of the cell cycle, overexpression of cyclin D1 will likely promote cells into cell cycle. This may further augment proliferation in addition to upregulated ABL1 kinase activity in the index case. It may also contribute to the resistance to imatinib, as imatinib only targets on BCR-ABL fusion. Therefore, the addition of t(11;14)(q13;q32) may have significant implication in patient management.
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PMID:Chronic myelogenous leukemia with acquired t(11;14)(q13;q32) CCND1-IGH: A case report and literature review. 2781 77

Lymphadenopathy in chronic myeloid leukemia (CML) is usually due to extramedullary involvement with accelerated or blast phases of the disease. The occurrence of non-Hodgkin lymphoma (NHL) as a synchronous malignancy with CML is rare. We report a case of a 73-year-old male who presented with dyspnea and right-sided lower extremity edema in the setting of leukocytosis. Bone marrow evaluation indicated a chronic phase chronic myeloid leukemia (CML), confirmed by molecular testing. Imaging of the chest for persistent dyspnea revealed supraclavicular and mediastinal lymphadenopathy. Biopsy of the cervical node showed expanded lymphoid follicles with atypical germinal centers that were positive for CD10, BCL-2, and BCL-6, consistent with follicular lymphoma (FL). Nodal PCR demonstrated clonal IGH and IGK gene rearrangements, and FISH analysis was positive for IGH-BCL-2 fusion. Together, these tests supported the diagnosis of FL. Additionally, the lymph node showed paracortical expansion by maturing pan-hematopoietic elements, no blastic groups, and positive RT-PCR analysis for BCR-ABL1, indicating concomitant involvement by chronic phase-CML. To our knowledge, this is the first reported case of a patient with a concurrent diagnosis of CML and FL.
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PMID:Concurrent Diagnosis of Chronic Myeloid Leukemia and Follicular Lymphoma: An Unreported Presentation. 3027 41

Chromosome 14 is the most frequently rearranged chromosome in non-Hodgkin lymphoma (NHL), with aberrations particularly involving the heavy-chain immunoglobulin gene (IGH) in the chromosome band 14q32. Several translocation partners have been described: t(14;18)(q32;21)/IGH-BCL2 in follicular lymphoma (FL), t(11;14)(q13;q32)/CCND1-IGH in mantle cell lymphoma, and t(8;14)(q24;q32)/MYC-IGH in Burkitt lymphoma. The chromosomal locus 22q11 contains two important genes associated with leukemia and lymphoma; one is BCR, which fuses with ABL from 9q34 in chronic myeloid leukemia, and the other is the immunoglobulin lambda gene (IGL), which is rarely involved in the translocations observed in B-cell NHL. The t(14;22)(q32;q11) translocation has been previously reported in 8 cases of B-cell NHL; however, the translocation between IGH and IGL has been experimentally confirmed using fluorescence in situ hybridization (FISH) for only 4 cases. Here, we describe the first case of FL with a t(14;22)(q32;q11)/IGH-IGL translocation confirmed using FISH analysis. The patient in our case report was immunocompromised and was treated for aplastic anemia with cyclosporine A (CsA). The patient was diagnosed with follicular lymphoma, most likely caused by CsA.
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PMID:A case study of t(14;22)(q32;q11) involving immunoglobulin heavy and light chain in follicular lymphoma. 3193 30