Blood MALT1 deficiency is common and relates to unfavorable induction therapy response and survival profile in acute myeloid leukemia patients

Figures & data

Table 1. Characteristics of AML patients.

Items	AML patients (N = 90)
Age (years), mean ± SD	57.5 ± 13.1
Gender, n (%)
Female	32 (35.6)
Male	58 (64.4)
WBC (10^9/L), median (IQR)	14.4 (8.1-29.3)
BM blasts (%), median (IQR)	76.0 (64.0-86.0)
FAB Classification, n (%)
M1	10 (11.1)
M2	24 (26.7)
M4	26 (28.9)
M5	25 (27.8)
M6	5 (5.5)
Cytogenetics, n (%)
NK	46 (51.1)
CK	11 (12.2)
inv(16) or t(16;16)	7 (7.8)
+8	5 (5.6)
t(9;11)	4 (4.4)
−7 or 7q-	2 (2.2)
−5 or 5q-	1 (1.1)
Others (not included in better or poor risk)	14 (15.6)
MK mutation, n (%)	5 (5.6)
FLT3-ITD mutation, n (%)	20 (22.2)
Isolated biallelic CEBPA mutation, n (%)	10 (11.1)
NPM1 mutation, n (%)	25 (27.8)
WT1 mutation, n (%)	11 (12.2)
Risk stratification, n (%)
Favorable	18 (20.0)
Intermediate	45 (50.0)
Poor	27 (30.0)

AML, acute myeloid leukemia; SD, standard deviation; WBC, white blood cell; BM, bone marrow; IQR, interquartile range; FAB classification, French-American-Britain classification; NK, normal karyotype; CK, complex karyotype; MK, monosomal karyotype; FLT3-ITD, internal tandem duplications in the FMS-like tyrosine kinase 3; CEBPA, CCAAT/enhancer-binding protein α; NPM1, nucleophosmin 1; WT1, Wilms’ Tumor 1.

Figure 1. MALT1 was reduced in AML patients compared to HCs and DCs. Comparison of MALT1 expression among AML patients, DCs, and HCs (A). ROC curve analyses of MALT1 expression in distinguishing AML patients from DCs (B); AML patients from HCs (C); DCs from HCs (D).

Table 2. Correlation of MALT1 expression with clinical characteristics in AML patients.

Items	MALT1 expression, median (IQR)	P value
Age		.965
≤60 years (median)	0.376 (0.239-0.574)
>60 years (median)	0.364 (0.187-0.595)
Gender		.631
Female	0.334 (0.227-0.577)
Male	0.385 (0.170-0.594)
WBC		.037
≤10×10^9/L	0.537 (0.270-0.643)
>10×10^9/L	0.314 (0.185-0.526)
BM blasts (%)		.047
Quartile 1	0.544 (0.227-0.761)
Quartile 2	0.416 (0.238-0.545)
Quartile 3	0.293 (0.181-0.593)
Quartile 4	0.269 (0.174-0.476)
FAB Classification		.097
M1	0.206 (0.136-0.304)
M2	0.405 (0.137-0.590)
M4	0.416 (0.226-0.592)
M5	0.394 (0.291-0.614)
M6	0.364 (0.117-0.884)
Cytogenetics		.301
NK	0.306 (0.167-0.525)
CK	0.310 (0.225-0.594)
inv(16) or t(16;16)	0.561 (0.303-0.605)
+8	0.393 (0.186-0.697)
t(9;11)	0.469 (0.372-0.764)
−7 or 7q-	0.284 (0.191-NR)
−5 or 5q-	NR (NR -NR)
Others	0.407 (0.208-0.653)
MK mutation		.398
No	0.376 (0.215-0.593)
Yes	0.310 (0.204-0.377)
FLT3-ITD mutation		.104
No	0.385 (0.234-0.600)
Yes	0.304 (0.139-0.474)
Isolated biallelic CEBPA mutation		.872
No	0.370 (0.212-0.593)
Yes	0.369 (0.226-0.508)
NPM1 mutation		.286
No	0.376 (0.215-0.602)
Yes	0.361 (0.204-0.513)
WT1 mutation		.249
No	0.377 (0.225-0.587)
Yes	0.229 (0.126-0.604)
Risk stratification		.020
Favorable	0.526 (0.284-0.601)
Intermediate	0.393 (0.233-0.596)
Poor	0.247 (0.139-0.448)

MALT1, Mucosa-associated lymphoid tissue lymphoma translocation protein 1; AML, acute myeloid leukemia; IQR, interquartile range; WBC, white blood cell; BM, bone marrow; FAB classification, French-American-Britain classification; NK, normal karyotype; CK, complex karyotype; NR, not reach; MK, monosomal karyotype; FLT3-ITD, internal tandem duplications in the FMS-like tyrosine kinase 3; CEBPA, CCAAT/enhancer-binding protein α; NPM1, nucleophosmin 1; WT1, Wilms’ Tumor 1.

Figure 2. MALT1 was elevated during induction treatment in AML patients. Comparison of pre-treatment and post-treatment MALT1 expression in total AML patients (A); in AML patients with CR (B); in AML patients with non-CR (C). Comparison of MALT1 expressions between AML patients with CR and AML patients with non-CR (D). Comparison of MALT1 expression increment (E) and MALT1 expression increment % (F) between AML patients with CR and AML patients with non-CR.

Figure 3. Pre-treatment and post-treatment MALT1 low expression were linked with unfavorable survival profile in AML patients. Correlation of pre-treatment MALT1 low (vs. high) (A) and pre-treatment MALT1 quartile (B) with accumulating EFS. Association of pre-treatment MALT1 low (vs. high) (C) and pre-treatment MALT1 quartile (D) with accumulating OS. Correlation of post-treatment MALT1 low (vs. high) (E) and post-treatment MALT1 quartile (F) with accumulating EFS. Association of post-treatment MALT1 low (vs. high) (G) and post-treatment MALT1 quartile with accumulating OS (H).

Figure 4. MATL1 increment < 50% was related to shorter accumulating EFS and OS in AML patients. Relationship between MALT1 increment < 50% (vs. increment ≥ 50%) and accumulating EFS (A) as well as accumulating OS (B).