Cell lineage involvement of recurrent chromosomal abnormalities in hematologic neoplasms

Abstract

Analysis of most hematologic neoplasms indicates the involvement of one or more cell lineages in the bone marrow and/or the blood but rules out the involvement of all lineages in any one neoplasm. It is important to detect lineage involvement in order to clarify which stem cells are involved in leukemia, to predict prognosis, and to select appropriate treatment. Our aim was to study the cell lineage involvement of some of the recurrent chromosomal abnormalities seen in hematological neoplasms. The direct morphology-antibody-chromosomes (MAC) method was used. The deletion 20q in myeloproliferative diseases (MPD), the deletion of 5q and t(1;7) in myelodysplastic syndromes (MDS), and t(3;3) in acute myeloid leukemia subtype M7 (AML-M7) were seen in all or at least in two myeloid lineages. These were interpreted as stem cell abnormalities. Deletion 13q in MPD, t(8;21) in AML-M2 and t(15;17) in AML-M3 were seen in granulocytic lineages only; t(14;18) in non-Hodgkin's lymphoma and trisomy 12 as the sole abnormality in chronic lymphocytic leukemia (B-CLL) were seen only in immunoglobulin light chain clonal B cells; inversion 14 in T-CLL was seen only in T cells, whereas t(15;14) in acute lymphocytic leukemia with eosinophilia (ALL-EO) was seen in lymphoid stem cells but not in mature granulocytes or lymphocytes. Additional abnormalities (in addition to the Philadelphia chromosome) in chronic myeloid leukemia (CML) were seen in all myeloid cell lineages and also in mature granulocytes, B cells, and large granular lymphocytes. Abnormalities in Hodgkin's disease were restricted to CD30-positive Reed-Sternberg cells. Trisomy 8 and monosomy 7 are abnormalities that may be present in either stem cells or any of the single cell lineages.

Pathogenetic insight and prognostic information from standard and molecular cytogenetic studies in the BCR-ABL-negative myeloproliferative neoplasms (MPNs)

“…In a patient with ET and 20qÀ, the deletion was detected in myeloid, erythroid, CD34 þ progenitor cells, as well as CD10 þ lymphoid cells. 129 Furthermore, a lymphoblastoid cell line derived from a patient with a Philadelphiapositive ALL contained the 20q deletion, as did the CFU-GM, CFU-GEMM and BFU-E. 130,131 These two reports imply that CMPDs may arise in an early progenitor cell with both myeloid and lymphoid potential. This conclusion is also supported by studies in PMF, in which the involvement of B and T cells has been documented.…”

Acute promyelocytic leukemia: where does it stem from?

“…66 Similarly, the t(15;17) was found to be restricted to the granulocytic series in an earlier study that utilized the MAC method (morphology-antibody-chromosomes). 67 However, two further studies yielded results with quite different implications regarding the origins of APL. In particular, Takatsuki et al 68 detected PML-RARA mRNA in BFU-E in 2/5 cases examined.…”

Cytogenetic analysis of CD34+ subpopulations in AML and MDS characterized by the expression of CD38 and CD117

“…Most is a reflection of the level of the hematopoietic hierarchy at which the leukemogenic genetic defect occurs. A new model information was derived from FISH and/or cytogenetic analyses of immunophenotypically characterized cells from differtaking into account recent stem cell data could be derived from the hypothesis that the genetic defect regularly occurs at ent cell lineages, [26][27][28][29] or from combining morphology and FISH. 30 Another group examined Ig heavy chain gene the level of immature pluripotent stem cells and determines the differentiation program of the affected cell clone.…”