Marrow fibrosis and its relevance during imatinib treatment of chronic myeloid leukemia

Abstract

In chronic myeloid leukemia (CML), imatinib may reverse bone marrow fibrosis (MF). Whether the unfavorable prognosis of MF is also reversed and whether imatinib guarantees against evolution of MF are unclear as yet. Fifty-nine patients with Ph þ CML treated with X400 mg imatinib/day were examined for MF in 6-to 12-month intervals. Imatinib effectively reversed initial MF (Po0.0005). However, during a follow-up period of up to 4.8 years, small foci with abnormal fiber increase (FFI) emerged in 8 of 30 pretreated and 6 of 29 non-pretreated patients. Patients with FFI showed a significantly lower probability of achieving a complete cytogenetic or major molecular response (36 versus 81%; Po0.007). During the further follow up, 57% of patients with FFI but none of the other patients suffered from full-blown MF (P ¼ 0.00005). None of the patients with FFI or MF showed a Janus kinase-2 mutation (V617F). Evolutions of FFI and MF were independent significant predictors of imatinib failure (P ¼ 0.0031), accelerated phase and death of patients (P ¼ 0.0001; multivariate analyses). Imatinib effectively reverses initial MF in CML, but neither eliminates its unfavorable prognosis nor guarantees completely against new evolution of MF.

The underestimated role of basophils in Ph+ chronic myeloid leukaemia

“…Moreover, increased angiogenesis and fibrosis in the bone marrow (BM) and other hematopoietic tissues have been associated with progression in CML 21, 22, 23, 24, 25, 26…”

Systemic mastocytosis (SM) with associated BCR-ABL-positive myelogenous leukaemia (SM-AHNMD): evidence that mast cells do not belong to the leukaemic clone

“…These secondary cytogenetic aberrations appear to be associated either with (1) persistent CML, (2) therapy-related hypoplastic or transient variants of the myelodysplastic syndromes, (3) a secondary acute leukaemia, (4) occasional fibrosis or with (5) no phenotypically detectable haematological disorders. 5,8 In the present case, the Ph þ clonality showed cytogenetic evolution but no secondary IM resistance-mediating BCR-ABL mutations and was associated with the persistence of the CML phenotype. Because the original Ph þ clone proliferated in parallel to its subclones, other additional subchromosomal mutations are likely.…”

“…Co-existence of CML and a non-CML neoplastic proliferation of myeloid origin is very rare. 4,5 A few cases of Ph þ CML with Ph À /JAK2 V617F myeloproliferative neoplasms (MPN) have been described. 4 CML can be suppressed by the BCR-ABL inhibitor imatinib mesylate (IM).…”

“…Fibrosis is not uncommon in CML and can be found in about 20% of cases. 5 Immunohistochemistry immediately unmasked the dense focal mast cell infiltrates within the desmoplastic matrix. Owing to its rarity, a systematic evaluation of concomitant SM in Ph þ CML cannot be recommended.…”

BMP et cancer

“…Elle se traduit par une désorganisation des fibres de collagène et de fibronectine induisant une rigidité accrue du tissu, un regroupement de certaines intégrines ainsi que l'activation anormale de certaines voies de signalisation [25]. La majorité des hémopathies malignes sont caracté-risées par une altération plus ou moins marquée de la composition de la moelle osseuse, avec le plus souvent une myélofibrose qui s'accentue avec la progression de la maladie [26]. Or les BMP sont connues pour leur implication dans les processus ostéogéniques.…”