Different suppression of Ph1 positive hemopoiesis induced by intensive chemotherapy in lymphoid and myeloid blast crisis of CML.
BACKGROUND
The suppression of Ph1-positive hemopoiesis is a major goal in the treatment of CML; in this context the CML patients in blast crisis obtaining a complete clinical remission represent a useful model to investigate the behavior of the Ph1-positive and negative clones during bone marrow repopulation after ablative therapy.


METHODS
Seven CML patients in blast crisis (four lymphoid and three myeloid) who obtained a complete clinical remission after an intensive polychemotherapy treatment were evaluated by cytogenetic and molecular analysis both in blast and remission phases. Standard cytogenetic and Southern techniques were employed; in addition, minimal residual disease status (MRD) was ascertained by amplification (PCR) of the specific bcr-abl chimeric transcripts.


RESULTS
After a single cycle of induction, all lymphoid cases displayed a complete restoration of Ph1-negative hemopoiesis; by contrast, one myeloid blast crisis showed a partial suppression of Ph1-positive hemopoiesis only after two cycles of chemotherapy, and in the remaining two cases the hematological remission was indeed a reversion to the chronic phase.


CONCLUSIONS
Ph1-positive chronic clones present in lymphoid blast crisis showed a higher degree of sensitivity to intensive chemotherapy than those present in the myeloid cases. This observation further suggests that the growth properties of the Ph1-positive clones are highly variable from case to case and probably tend to progress during the time-course of the disease.
Dipartimento di Scienze Biomediche e Oncologia Umana, Università di Torino, Italy.
A
A
Guerrasio
G
G
Martinelli
A
A
Ambrosetti
M
M
Falda
F
F
Paolino
G
G
Rege-Cambrin
C
C
Rosso
P F
PF
Pignatti
P
P
Gasparini
G
G
Perona
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D001752:Blast Crisis / Q000188:drug therapy* / Q000235:genetics; D002999:Clone Cells / Q000187:drug effects; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D015321:Gene Rearrangement; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D016133:Polymerase Chain Reaction
D016044:Fusion Proteins, bcr-abl