Cell lineage heterogeneity in blast crisis of chronic myeloid leukaemia

Abstract

Blast cells from 45 patients with chronic myeloid leukaemia in blast crisis (CML-BC) were immunologically phenotyped with a panel of 26 monoclonal antibodies and studied for terminal deoxynucleotidyl transferase (TdT) content. Out of 45 blast-populations, 28 showed a myeloid, 14 a lymphoid, two a mixed and one an unclassifiable marker profile. In contrast to acute myeloid leukaemia (AML), we found frequent involvement of the thrombopoietic and erythropoietic systems in myeloid CML-BC. Furthermore, the marker profile on blast cells in myeloid CML-BC was different from that seen in AML. The blast cells in lymphoid blast crises of CML displayed the same lymphoid marker profile as those in acute lymphoblastic leukaemia. In three of 16 patients who were serially tested, we observed phenotypic changes in the blast cell populations. In one patient the blasts changed from lymphoid to myeloid type while remaining TdT-positive; in another case the blasts switched from granulomonocytic TdT-negative to granulomonocytic TdT-positive. In the third patient erythroid precursor cells appeared as the disease progressed. The results indicate the capacity of blast populations in CML-patients during blast crisis to differentiate along several pathways.

Which compartments are involved in Philadelphia‐chromosome positive chronic myeloid leukaemia? An answer at the single cell level by combining May‐Grünwald‐Giemsa staining and fluorescence in situ hybridization techniques

“…Although involvement of B lymphocytes (Bettelheim et al, 1985;LeBien et al, 1979;Greaves et al, 1979;Bakhshi et al, 1983) or T cells (Allouche et al, 1985;Hernandez et al, 1982;Griffin et al, 1983;Sun et al, 1991;Kuriyama et al, 1989) in CML blast crisis is well known, direct evidence of involvement of B or T lymphocytes in the chronic phase of CML is inconclusive. Some authors were able to demonstrate the involvement of B lymphocytes (Martin et al, 1980;Bernheim et al, 1981;Nitta et al, 1985;Fauser et al, 1985;MacKinney et al, 1993;Tefferi et al, 1995), whereas others were not (Ferraris et al, 1989).…”

“…Even the lymphocytic lineage might be involved because both myeloid and lymphatic blast crisis are observed at final stages of the disease (Bettelheim et al, 1985). However, involvement of the B and T lymphocytes in the neoplastic process remains controversial.…”

p210BCR-ABL reprograms transformed and normal human megakaryocytic progenitor cells into erythroid cells and suppresses FLI-1 transcription

“…In the chronic phase, one of the major biological abnormalities is an increased production of morphologically mature granulocytes. 4 This phase is also characterized by an abnormal, unregulated expansion of Philadelphia chromosome-positive (Ph þ ) primitive erythroid progenitors, both in bone marrow and in peripheral blood. 5 In addition, occasional examples of Ph þ patients presenting with an erythrocytosis have been reported.…”

“…6 Further evidence for an abnormal erythroid differentiation is suggested by an unexpectedly frequent occurrence of blast cells with erythropoietic and/or megakaryocytic surface determinants in non-lymphoid blast crises. 4 Moreover, most cell lines established from CML blast crisis patients exhibit some erythroid and/ or megakaryocytic characters. [7][8][9] These results strongly point to a critical role of BCR-ABL in acting upon erythroid and/or megakaryocytic development.…”

ABL gene kinase domain mutation scanning by denaturing high performance liquid chromatography sequencing method

“…The clinical course of CML is characteristically triphasic, starting with a chronic phase (CP) of variable duration, followed by progression to an accelerated phase (AP) and finally resulting in blast crises (BC) [3][4][5]. CML is the first discovered human cancer associated with a consistent chromosomal abnormality-the chimeric BCR/ABL gene, known as Philadelphia (Ph) chromosome [6,7].…”