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Philadelphia chromosome-negative chronic myelogenous leukemia without breakpoint cluster region rearrangement: a chronic myeloid leukemia with a distinct clinical course.
Blood 1990; 75(2):445-52Blood

Abstract

The hallmarks of chronic myelogenous leukemia (CML) include the Philadelphia chromosome (Ph) translocation [t (9;22)(q34;q11)] and consistent molecular genetic aberrations: a break within a restricted 5.8 kb DNA segment, bcr, on chromosome 22q11; transposition of the c-abl protooncogene from chromosome 9q34 to 22q11; and formation of a hybrid bar-abl gene encoding an abnormal 210 Kd bcr-abl protein with augmented tyrosine kinase enzymatic activity. These molecular phenomena may occur even in the absence of cytogenetic evidence of the Ph translocation. They are highly specific and sensitive markers for CML, and are presumed to play a significant role in the pathogenesis of this malignancy. Surprisingly, we have encountered 11 patients who lacked the Ph translocation, bcr rearrangement, and (in the four patients with available mRNA) a bcr-abl message, and yet had a disease phenotype at diagnosis that was a morphologic facsimile of classic chronic phase CML. These patients presented with high white blood cell counts, neutrophilia, occasional basophilia, splenomegaly, and a hypercellular bone marrow with granulocytic hyperplasia and a left shift in myeloid maturation. Despite the striking resemblance between the early stages of bcr-negative and bcr-positive CML, disease progression manifests distinctly in these two disorders. In contrast to the blastic transformation that inevitably complicates bcr-positive CML, the natural history of our 11 Ph-negative, bcr-negative CML patients was characterized by increasing leukemia burden with leukocytosis, pronounced organomegaly, extramedullary infiltrates, and eventual bone marrow failure (anemia and thrombocytopenia) without marked increases in blast cells. Our current observations suggest that a chronic myeloid leukemia process can develop without associated changes in the bcr or c-abl genes. Although the initial phase of this disease is indistinguishable from CML, the presence or absence of molecular markers may aid in the prediction of the clinical course of Ph-negative CML.

Authors+Show Affiliations

Department of Clinical Immunology and Biological Therapy, UT M.D. Anderson Cancer Center, Houston 77030.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

2403827

Citation

Kurzrock, R, et al. "Philadelphia Chromosome-negative Chronic Myelogenous Leukemia Without Breakpoint Cluster Region Rearrangement: a Chronic Myeloid Leukemia With a Distinct Clinical Course." Blood, vol. 75, no. 2, 1990, pp. 445-52.
Kurzrock R, Kantarjian HM, Shtalrid M, et al. Philadelphia chromosome-negative chronic myelogenous leukemia without breakpoint cluster region rearrangement: a chronic myeloid leukemia with a distinct clinical course. Blood. 1990;75(2):445-52.
Kurzrock, R., Kantarjian, H. M., Shtalrid, M., Gutterman, J. U., & Talpaz, M. (1990). Philadelphia chromosome-negative chronic myelogenous leukemia without breakpoint cluster region rearrangement: a chronic myeloid leukemia with a distinct clinical course. Blood, 75(2), pp. 445-52.
Kurzrock R, et al. Philadelphia Chromosome-negative Chronic Myelogenous Leukemia Without Breakpoint Cluster Region Rearrangement: a Chronic Myeloid Leukemia With a Distinct Clinical Course. Blood. 1990 Jan 15;75(2):445-52. PubMed PMID: 2403827.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Philadelphia chromosome-negative chronic myelogenous leukemia without breakpoint cluster region rearrangement: a chronic myeloid leukemia with a distinct clinical course. AU - Kurzrock,R, AU - Kantarjian,H M, AU - Shtalrid,M, AU - Gutterman,J U, AU - Talpaz,M, PY - 1990/1/15/pubmed PY - 1990/1/15/medline PY - 1990/1/15/entrez SP - 445 EP - 52 JF - Blood JO - Blood VL - 75 IS - 2 N2 - The hallmarks of chronic myelogenous leukemia (CML) include the Philadelphia chromosome (Ph) translocation [t (9;22)(q34;q11)] and consistent molecular genetic aberrations: a break within a restricted 5.8 kb DNA segment, bcr, on chromosome 22q11; transposition of the c-abl protooncogene from chromosome 9q34 to 22q11; and formation of a hybrid bar-abl gene encoding an abnormal 210 Kd bcr-abl protein with augmented tyrosine kinase enzymatic activity. These molecular phenomena may occur even in the absence of cytogenetic evidence of the Ph translocation. They are highly specific and sensitive markers for CML, and are presumed to play a significant role in the pathogenesis of this malignancy. Surprisingly, we have encountered 11 patients who lacked the Ph translocation, bcr rearrangement, and (in the four patients with available mRNA) a bcr-abl message, and yet had a disease phenotype at diagnosis that was a morphologic facsimile of classic chronic phase CML. These patients presented with high white blood cell counts, neutrophilia, occasional basophilia, splenomegaly, and a hypercellular bone marrow with granulocytic hyperplasia and a left shift in myeloid maturation. Despite the striking resemblance between the early stages of bcr-negative and bcr-positive CML, disease progression manifests distinctly in these two disorders. In contrast to the blastic transformation that inevitably complicates bcr-positive CML, the natural history of our 11 Ph-negative, bcr-negative CML patients was characterized by increasing leukemia burden with leukocytosis, pronounced organomegaly, extramedullary infiltrates, and eventual bone marrow failure (anemia and thrombocytopenia) without marked increases in blast cells. Our current observations suggest that a chronic myeloid leukemia process can develop without associated changes in the bcr or c-abl genes. Although the initial phase of this disease is indistinguishable from CML, the presence or absence of molecular markers may aid in the prediction of the clinical course of Ph-negative CML. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/2403827/Philadelphia_chromosome_negative_chronic_myelogenous_leukemia_without_breakpoint_cluster_region_rearrangement:_a_chronic_myeloid_leukemia_with_a_distinct_clinical_course_ L2 - http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=2403827 DB - PRIME DP - Unbound Medicine ER -